Greenwich Hospital

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

BACKGROUND: The comparative effectiveness of performing instrumented (rigid pedicle screws affixed to titanium alloy rods) lumbar spinal fusion in addition to decompressive laminectomy in patients with symptomatic lumbar grade I degenerative spondylolisthesis with spinal stenosis is unknown. METHODS: In this randomized, controlled trial, we assigned patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone (decompression-alone group) or laminectomy with posterolateral instrumented fusion (fusion group). The primary outcome measure was the change in the physical-component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; range, 0 to 100, with higher scores indicating better quality of life) 2 years after surgery. The secondary outcome measure was the score on the Oswestry Disability Index (range, 0 to 100, with higher scores indicating more disability related to back pain). Patients were followed for 4 years. RESULTS: A total of 66 patients (mean age, 67 years; 80% women) underwent randomization. The rate of follow-up was 89% at 1 year, 86% at 2 years, and 68% at 4 years. The fusion group had a greater increase in SF-36 physical-component summary scores at 2 years after surgery than did the decompression-alone group (15.2 vs. 9.5, for a difference of 5.7; 95% confidence interval, 0.1 to 11.3; P=0.046). The increases in the SF-36 physical-component summary scores in the fusion group remained greater than those in the decompression-alone group at 3 years and at 4 years (P=0.02 for both years). With respect to reductions in disability related to back pain, the changes in the Oswestry Disability Index scores at 2 years after surgery did not differ significantly between the study groups (-17.9 in the decompression-alone group and -26.3 in the fusion group, P=0.06). More blood loss and longer hospital stays occurred in the fusion group than in the decompression-alone group (P<0.001 for both comparisons). The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group (P=0.05). CONCLUSIONS: Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).

OBJECTIVE: To investigate the safety and efficacy of MRA, a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL-6, in patients with established rheumatoid arthritis (RA). METHODS: A randomized, double-blind, placebo-controlled, dose-escalation trial was conducted in 45 patients with active RA, as defined by the American College of Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive a single intravenous dose of either 0.1, 1, 5, or 10 mg/kg of MRA or placebo. The primary efficacy end point was meeting the ACR 20% response criteria at week 2 after treatment. RESULTS: Demographic features were similar between treatment groups. At week 2, a significant treatment difference was observed between the 5 mg/kg of MRA and placebo, with 5 patients (55.6%) in the MRA cohort and none in the placebo cohort achieving ACR 20% improvement. There was no statistically significant difference in the ACR 20% response between the other 3 MRA cohorts and placebo at week 2. The mean disease activity score at week 2 in those who received 5 mg/kg and 10 mg/kg of MRA was 4.8 and 4.7 (P < 0.001 and P < 0.001 by analysis of variance), respectively. These mean scores were statistically significantly lower than those in the 0.1- and 1-mg/kg MRA and the placebo cohorts (6.4, 6.2, and 7.0, respectively). The erythrocyte sedimentation rate and C-reactive protein values fell significantly in the 5- and 10-mg/kg MRA cohorts and normalized 2 weeks after treatment. Seventeen patients (5, 4, 6, 2, and 0 patients in the placebo, 0.1-, 1-, 5-, and 10-mg/kg MRA cohorts, respectively) required corticosteroid or disease-modifying antirheumatic drug treatment because of active disease before study end. They were regarded as nonresponders from the time they received these treatments. Diarrhea was the most common adverse event, occurring in 8% of patients. Seven patients (15.6%) reported a severe adverse event (3, 1, 2, and 2 patients in the placebo, 0.1-, 1-, and 10-mg/kg MRA cohorts). There were no serious adverse events that were thought to be related to the study drug. CONCLUSION: This is the first randomized controlled trial showing that inhibition of IL-6 significantly improved the signs and symptoms of RA and normalized the acute-phase reactants. Further research with multiple dosing is necessary to define the most appropriate therapeutic regimen of MRA in RA.

PURPOSE: To determine the response rate, time to disease progression, survival duration and rate, and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer. PATIENTS AND METHODS: Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial. Patients were treated with cetuximab at an initial dose of 400 mg/m(2), followed by 250 mg/m(2) weekly for 7 weeks. Gemcitabine was administered at 1,000 mg/m(2) for 7 weeks, followed by 1 week of rest. In subsequent cycles, cetuximab was administered weekly, and gemcitabine was administered weekly for 3 weeks every 4 weeks. RESULTS: Sixty-one patients were screened for EGFR expression, 58 patients (95%) had at least 1+ staining, and 41 were enrolled onto the trial. Five patients (12.2%) achieved a partial response, and 26 (63.4%) had stable disease. The median time to disease progression was 3.8 months, and the median overall survival duration was 7.1 months. One-year progression-free survival and overall survival rates were 12% and 31.7%, respectively. The most frequently reported grade 3 or 4 adverse events were neutropenia (39.0%), asthenia (22.0%), abdominal pain (22.0%), and thrombocytopenia (17.1%). CONCLUSION: Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer. Further clinical investigation is warranted.

BACKGROUND: Refugees who have suffered traumatic events present complex therapeutic challenges to health professionals. There is little research into post-exile factors that may be amenable to change, and therefore reduce morbidity. We examined the importance of social factors in exile and of trauma factors in producing the different elements of psychological sequelae of severe trauma. METHOD: Eighty-four male Iraqi refugees were interviewed. Adverse events and level of social support were measured. Various measures of psychological morbidity were applied, all of which have been used in previous trauma research. RESULTS: Social factors in exile, particularly the level of "affective" social support, proved important in determining the severity of both post-traumatic stress disorder and depressive reactions, particularly when combined with a severe level of trauma/torture. Poor social support is a stronger predictor of depressive morbidity than trauma factors. CONCLUSIONS: Some of the most important factors in producing psychological morbidity in refugees may be alleviated by planned, integrated rehabilitation programmes and attention to social support and family reunion.

We study three cases in which specialized arbitrageurs lost significant amounts of capital and, as a result, became liquidity demanders rather than providers. The effects on security markets were large and persistent: Prices dropped relative to fundamentals and the rebound took months. While multi-strategy hedge funds who were not capital constrained increased their positions, a large fraction of these funds actually acted as net sellers consistent with the view that information barriers within a firm (not just relative to outside investors) can lead to capital constraints for trading desks with mark-to-market losses. Our findings suggest that real world frictions impede arbitrage capital.

BACKGROUND: Declining serum concentrations of 25-hydroxyvitamin D seen in the fall and winter as distance increases from the equator may be a factor in the seasonal increased prevalence of influenza and other viral infections. This study was done to determine if serum 25-hydroxyvitamin D concentrations correlated with the incidence of acute viral respiratory tract infections. METHODOLOGY/FINDINGS: In this prospective cohort study serial monthly concentrations of 25-hydroxyvitamin D were measured over the fall and winter 2009-2010 in 198 healthy adults, blinded to the nature of the substance being measured. The participants were evaluated for the development of any acute respiratory tract infections by investigators blinded to the 25-hydroxyvitamin D concentrations. The incidence of infection in participants with different concentrations of vitamin D was determined. One hundred ninety-five (98.5%) of the enrolled participants completed the study. Light skin pigmentation, lean body mass, and supplementation with vitamin D were found to correlate with higher concentrations of 25-hydroxyvitamin D. Concentrations of 38 ng/ml or more were associated with a significant (p<0.0001) two-fold reduction in the risk of developing acute respiratory tract infections and with a marked reduction in the percentages of days ill. CONCLUSIONS/SIGNIFICANCE: Maintenance of a 25-hydroxyvitamin D serum concentration of 38 ng/ml or higher should significantly reduce the incidence of acute viral respiratory tract infections and the burden of illness caused thereby, at least during the fall and winter in temperate zones. The findings of the present study provide direction for and call for future interventional studies examining the efficacy of vitamin D supplementation in reducing the incidence and severity of specific viral infections, including influenza, in the general population and in subpopulations with lower 25-hydroxyvitamin D concentrations, such as pregnant women, dark skinned individuals, and the obese.

N-acetylcysteine (NAC), the acetylated variant of the amino acid L-cysteine, is an excellent source of sulfhydryl (SH) groups, and is converted in the body into metabolites capable of stimulating glutathione (GSH) synthesis, promoting detoxification, and acting directly as free radical scavengers. Administration of NAC has historically been as a mucolytic agent in a variety of respiratory illnesses; however, it appears to also have beneficial effects in conditions characterized by decreased GSH or oxidative stress, such as HIV infection, cancer, heart disease, and cigarette smoking. An 18-dose oral course of NAC is currently the mainstay of treatment for acetaminophen-induced hepatotoxicity. N-acetylcysteine also appears to have some clinical usefulness as a chelating agent in the treatment of acute heavy metal poisoning, both as an agent capable of protecting the liver and kidney from damage and as an intervention to enhance elimination of the metals.

Alcohol misuse and alcohol withdrawal are associated with a variety of neuropsychiatric syndromes, some of which are associated with significant morbidity and mortality. B vitamin deficiency is known to contribute to the aetiology of a number of these syndromes, and B vitamin supplementation thus plays a significant part in prophylaxis and treatment. In particular, the Wernicke Korsakoff syndrome (WKS). due to thiamine deficiency, is a common condition in association with alcohol misuse, and is associated with high morbidity and mortality. Nicotinamide deficiency may result in a rarer condition, alcoholic pellagra encephalopathy, which often has a similar clinical presentation to WKS. This review considers the role of B vitamins in the aetiology and treatment of neuropsychiatric syndromes associated with alcohol misuse, with particular emphasis on WKS.

The classic signs of vitamin deficiency only occur in states of extreme depletion and are unreliable indicators for early treatment or prophylaxis of alcoholic patients at risk. Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80–90% of these patients. The causes of vitamin deficiency are reviewed with special attention to the inhibition of oral thiamine hydrochloride absorption in man caused by malnutrition present in alcoholic patients or by the direct effects of ethanol on intestinal transport. As the condition of the patient misusing alcohol progresses, damage to brain, liver, gastrointestinal tract, and pancreas continue (with other factors discussed) to further compromise the patient. Decreased intake, malabsorption, reduced storage, and impaired utilization further reduce the chances of unaided recovery. Failure of large oral doses of thiamine hydrochloride to provide an effective treatment for Wernicke's encephalopathy emphasizes the need for adequate and rapid replacement of depleted brain thiamine levels by repeated parenteral therapy in adequate doses.

We study the nature of sovereign credit risk using an extensive sample of CDS spreads for 26 developed and emerging-market countries. Sovereign credit spreads are surprisingly highly correlated, with just three principal components accounting for more than 50 percent of their variation. Sovereign credit spreads are generally more related to the U.S. stock and high-yield bond markets, global risk premia, and capital flows than they are to their own local economic measures. We find that the excess returns from investing in sovereign credit are largely compensation for bearing global risk, and that there is little or no country-specific credit risk premium. A significant amount of the variation in sovereign credit returns can be forecast using U.S. equity, volatility, and bond market risk premia.

BACKGROUND: Despite an increase in the prevalence of medial ulnar collateral ligament (UCL) reconstruction of the elbow in professional baseball and popularity within the media, there are no population-based studies examining the incidence of UCL reconstruction. PURPOSE: To examine the epidemiological trends of UCL reconstruction on a statewide level over a 10-year period. The primary endpoint was the yearly rate of UCL reconstruction over time; secondary endpoints included patient demographics, institution volumes, and concomitant procedures on the ulnar nerve. STUDY DESIGN: Descriptive epidemiology study. METHODS: The New York Statewide Planning and Research Cooperative System (SPARCS) database contains records for each ambulatory discharge in New York State. This database was used to identify all UCL reconstructions in New York State from 2002 to 2011 using the outpatient CPT-4 (Current Procedural Terminology, 4th Revision) code. Assessed were patient age, sex, ethnicity, insurance status, and associated procedures, as well as hospital volume. RESULTS: There was a significant yearly increase in the number of UCL reconstructions (P < .001) performed in New York State from 2002 to 2011. The volume of UCL reconstructions increased by 193%, and the rate per 100,000 population tripled from 0.15 to 0.45. The mean ± SD age was 21.6 ± 8.89 years, and there was a significant trend for an increased frequency in UCL reconstruction in patients aged 17 to 18 and 19 to 20 years (P < .001). Male patients were 11.8 times more likely to have a UCL reconstruction than female patients (P < .001), and individuals with private insurance were 25 times more likely to have a UCL reconstruction than those with Medicaid (P = .0014). There was a 400% increase in concomitant ulnar nerve release/transposition performed over time in the study period, representing a significant increase in the frequency of ulnar nerve procedures at the time of UCL reconstruction (P < .001). CONCLUSION: The frequency of UCL reconstruction is steadily rising in New York State and becoming more common in adolescent athletes. Emphasis on public education on the risks of overuse throwing injuries and the importance of adhering to preventative guidelines is essential in youth baseball today.

SUMMARY One‐hundred‐and‐sixty‐six children whose blood lead levels had previously been determined were assessed on a battery of psychometric tests. Blood lead levels ranged from 7 to 33μg/100ml, and the group performed within the average range on all tests of attainment and intelligence. There were significant associations between blood lead levels and attainment scores on tests of reading, spelling and intelligence, but not on mathematics. These differences in performances largely remained after social class was partialled out. Partial correlation and multiple regression analyses suggest that while only a small proportion of the variance in intelligence is explained by blood lead levels, this relationship, is independent of social class. Caution is necessary in interpreting these findings, in view of the crude measure of social factors available. RÉSUMÉ Relation entre la concentration sanguine de plomb, l'intelligence et le niveau de réussite dans une population scolaire: étude pilote Un total de 166 enfants dont les taux sanguins de plomb avaient préalablement été mesurés ont béneficié d'une batterie de tests psychometfiques. Les taux sanguins de plomb variaient entre 7 et 33μg/ml et l'ensemble du groupe se situait dans la moyenne pour tous les tests d'intelligence et de réussite. II a été observé des liens significatifs entre les taux sanguins de plomb et les scores obtenus aux tests de lecture, orthographe et intelligence, mais non de mathématiques. Ces différences de performances persistent largement après correction de l'effet classe sociale. Les corrélations partielles et les analyses de régression multiple suggèrent que si seule une faible proportion de la variance d'intelligence est expliquée par le taux sanguinde plomb, cette relation est indépendantede la classe sociale. Cependant, une prudence d'interprétation est necessaire du fait du caractere grossier de la mesure des facteurs sociaux utilisables. ZUSAMMENFASSUNG Relation zwischen Bleikonzentration im Blut, Intelligenz und Schulleistung. Eine Pilot Studie Insgesamt 166 Kinder, deren Blutbleigehalt zuvor bestimmt worden war, wurden einer Reihe von psychometrischen Tests unterzogen. Der Bleigehalt im Blut lag zwischen sieben und 33μg/ 100ml, die Gruppe schnitt bei alien Leistungs‐ und Intelligenztests durch‐schnittlich ab. Es fanden sich signifikante Beziehungen zwischen Blutbleispiegeln und Leistungen bei den Tests für Lesen, Buchstabieren und Intelligenz, nicht aber für Mathematik. Diese Unterschiede blieben weitgehend bestehen, nachdem soziale Einflüsse ausgeschlossen waren. Partialkorrelationen und multiple Regressions‐analysen deuten darauf hin, daß nur ein kleiner Teil der Veränderungen bei der Intelligenz durch Blutbleispiegel erklärt wird, während diese Beziehung vom sozialen Stand unabhängig ist. Da die Beurteilung der sozialen Faktoren nur ungenau sein kann, muß die Interpretation der Befunde zurückhaltend erfolgen. RESUMEN Relación entre la concentración de plomo en sangre, la inteligencia y al adelanto escolar en una población escolar: estudio piloto Un total de 166 ni&amp;#x006e;&amp;#x030a;os cuya concentracion de plomo en sangre había sido previamente determinada, fué evaluado por medio de una batería de tests psicométricos. Los niveles de plomo en sangre oscilaban entre 7 y 33μg/100ml, y el grupo se comportó dentro del margen promedio en todos los tests de inteligencia y de adelanto escolar. Había asociaciones significativas entre el nivel de plomo en sangre y los pun tajes de adelanto en los tests de lectura, deletreo e inteligencia, pero no en las matemáticas. Estas diferencias en la realización se conservaban después de eliminar parcialmente las diferencias sociales. La correlación parcial y los análisis múltiples de regresión sugieren que mientras que solo una pequeña proporción de variation en la inteligencia se explica por los niveles de plomo en sangre, esta relacion es independiente de la clase social. Es necesario ser cauteloso al interpretar los hallazgos en vista de las mediciones poco precisas que pueden utilizarse para los factores sociales.

PURPOSE: A clinical pathway for anxiety and depression in adult cancer patients was developed to guide best practice in Australia. METHODS: The pathway was based on a rapid review of existing guidelines, systematic reviews and meta-analyses, stakeholder interviews, a Delphi process with 87 multidisciplinary stakeholders and input from a multidisciplinary advisory panel. RESULTS: The pathway recommends formalized routine screening for anxiety and depression in patients with cancer at key points in the patient's journey. The Edmonton Symptom Assessment System or distress thermometer with problem checklist is recommended as brief screening tools, combined with a more detailed tool, such as the Hospital Anxiety and Depression Scale, to identify possible cases. A structured clinical interview will be required to confirm diagnosis. When anxiety or depression is identified, it is recommended that one person in a treating team takes responsibility for coordinating appropriate assessment, referral and follow-up (not necessarily carrying these out themselves). A stepped care model of intervention is proposed, beginning with the least intensive available that is still likely to provide significant health gain. The exact intervention, treatment length and follow-up timelines, as well as professionals involved, are provided as a guide only. Each service should identify their own referral network based on local resources and current service structure, as well as patient preference. DISCUSSION: This clinical pathway will assist cancer services to design their own systems to detect and manage anxiety and depression in their patients, to improve the quality of care.

Better understanding of surgical timing, improved surgical technique, and advanced rehabilitation protocols has led to decreased incidence of motion loss after anterior cruciate ligament injury and reconstruction. However, motion loss from high-energy, multiligament injuries continues to compromise functional outcome. Prevention, consisting of control of inflammation and early motion, remains the key element in avoiding motion loss. However, certain techniques, such as manipulation under anesthesia in conjunction with arthroscopic lysis of adhesions, are reliable treatment options. Open surgical débridement is rarely necessary and should be considered only as a salvage procedure. A greater understanding of the pathogenesis of arthrofibrosis and related inflammatory mediators may result in novel therapies for treating the patient with motion loss.

In its quest for knowledge, nursing has relied heavily on the positivist approach to scientific enquiry. Phenomenological enquiry identifies the essence of a phenomenon and accurately describes it through the lived experience. Through consistency in the use of the methodology, and avoidance of method slurring, academic rigour can be maintained. It is advocated that the phenomenological method is congruent with nursing ideals where humanistic knowledge is valued. Nurses and phenomenologists share skills in observation, interviewing, interaction and interpersonal relationships in the appreciation of the individual's perception of an experience. Through the development of professional practice, nurses thus gain the tools to assist them in phenomenological research. It is suggested that, given appropriate attention to rigour, phenomenological methodology could become the basic instrument in the reform of nursing research as it moves from the positivist to the humanist paradigm.

BACKGROUND: Eating disorders in children and adolescents remain a serious cause of morbidity and mortality in children, adolescents, and young adults. The working knowledge of pathophysiology, recognition, and management of eating disorders continues to evolve as research in this field continues. OBJECTIVES: This article builds on previous background and position papers outlining issues relevant to the care of the adolescent patient with an eating disorder. METHODS: The eating disorder special interest group from the Society for Adolescent Medicine recognized the need to update the state of the art published guidelines for the care of the adolescent patient with an eating disorder. This article was a multidisciplinary, group effort to summarize the current knowledge of best practice in the field. RESULTS: This article summarizes newer findings on pathogenesis and etiology, prevention and screening, risk factors, nutritional issues, care from the primary care clinician's perspective, appropriate use of a multidisciplinary team, and issues of managed care and reimbursement. CONCLUSIONS: Primary prevention combined with early recognition and treatment helps decrease morbidity and mortality in adolescents with eating disorders.

OBJECT: There is considerable debate among spine surgeons regarding whether fusion should be used to augment decompressive surgery in patients with symptomatic lumbar spinal stenosis involving Grade I degenerative spondylolisthesis. The authors prospectively evaluated the outcomes of patients treated between 2000 and 2002 at two institutions to determine whether fusion improves functional outcome 1 year after surgery. METHODS: Patients ranged in age from 50 to 81 years. They presented with degenerative Grade I (3- to 14-mm) spondylolisthesis and lumbar stenosis without gross instability (< 3 mm of motion at the level of subluxation). Those in whom previous surgery had been performed at the level of subluxation were excluded. Each patient completed Oswestry Disability Index (ODI) and Short Form-36 (SF-36) questionnaires preoperatively and at 6 to 12 months postoperatively. Some patients underwent decompression alone (20 cases), whereas others underwent decompression and posterolateral instrumentation-assisted fusion (14 cases), at the treating surgeon's discretion. Baseline demographic data, radiographic features, and ODI and SF-36 scores were similar in both groups. The 1-year fusion rate was 93%. Both forms of surgery independently improved outcome compared with baseline status, based on ODI and SF-36 physical component summary (PCS) results (p < 0.001). Decompression combined with fusion led to an improvement in ODI scores of 27.5 points, whereas decompression alone was associated with a 13.6-point increase (p = 0.02). Analysis of the SF-36 PCS data also demonstrated a significant intergroup difference (p = 0.003). CONCLUSIONS: Surgery substantially improved 1-year outcomes based on established outcomes instruments in patients with Grade I spondylolisthesis and stenosis. Fusion was associated with greater functional improvement.

Thyroid transcription factor-1 (TTF-1) is a 38-kd homeodomain containing DNA-binding protein originally identified in follicular cells of the thyroid and subsequently in pneumocytes. This review focuses on the utility of antisera in TTF-1 immunohistochemical staining in the diagnosis of neoplastic conditions. Based on published studies to date, anti-TTF-1 is a very useful reagent in distinguishing pulmonary adenocarcinoma from other primary carcinomas, identifying differentiated thyroid neoplasms, distinguishing mesothelioma from pulmonary adenocarcinoma, and distinguishing small cell carcinoma of the lung from Merkel cell carcinoma. It may also be useful in distinguishing neuroendocrine (NE) tumors of the lung from well-differentiated NE tumors from other sites, such as the intestine.

In this article, the authors study the performance of trend-following investing across global markets since 1880, extending the existing evidence by more than 100 years using a novel data set. They find that in each decade since 1880, time-series momentum has delivered positive average returns with low correlations to traditional asset classes. Further, time-series momentum has performed well in 8 out of 10 of the largest crisis periods over the century, defined as the largest drawdowns for a 60/40 stock/bond portfolio. Lastly, the authors find that time-series momentum has performed well across different macro environments, including recessions and booms, war and peace, high- and low-interest-rate regimes, and high- and low-inflation periods. <b>TOPICS:</b>Real assets/alternative investments/private equity, analysis of individual factors/risk premia, emerging, performance measurement