The pulmonary artery catheter: in medio virtus

OBJECTIVE: To clarify the role of the pulmonary artery catheter in the intensive care unit. DATA SOURCES: Recent and relevant literature from MEDLINE and authors' personal databases. STUDY SELECTION: Studies on pulmonary artery catheter use and use of other monitoring devices in critically ill patients. DATA EXTRACTION: Based largely on clinical experience and assessment of the relevant published literature and in response to recent articles attacking the pulmonary artery catheter, we propose that the pulmonary artery catheter is still a valuable tool for the hemodynamic monitoring of patients with complex disease processes in whom the information obtained from the pulmonary artery catheter may influence management. We suggest that there is a need to revisit the basics of hemodynamic management and reassess the way in which the pulmonary artery catheter is used, applying three key principles: correct measurement, correct data interpretation, and correct application. CONCLUSION: The pulmonary artery catheter is still a valuable tool for hemodynamic monitoring when used in selected patients and by physicians adequately trained to correctly interpret and apply the data provided.

The effects of excluding patients from the analysis in randomised controlled trials: meta-epidemiological study

OBJECTIVE: To examine whether excluding patients from the analysis of randomised trials are associated with biased estimates of treatment effects and higher heterogeneity between trials. DESIGN: Meta-epidemiological study based on a collection of meta-analyses of randomised trials. DATA SOURCES: 14 meta-analyses including 167 trials that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patient reported pain as an outcome. METHODS: Effect sizes were calculated from differences in means of pain intensity between groups at the end of follow-up, divided by the pooled standard deviation. Trials were combined by using random effects meta-analysis. Estimates of treatment effects were compared between trials with and trials without exclusions from the analysis, and the impact of restricting meta-analyses to trials without exclusions was assessed. RESULTS: 39 trials (23%) had included all patients in the analysis. In 128 trials (77%) some patients were excluded from the analysis. Effect sizes from trials with exclusions tended to be more beneficial than those from trials without exclusions (difference -0.13, 95% confidence interval -0.29 to 0.04). However, estimates of bias between individual meta-analyses varied considerably (tau(2)=0.07). Tests of interaction between exclusions from the analysis and estimates of treatment effects were positive in five meta-analyses. Stratified analyses indicated that differences in effect sizes between trials with and trials without exclusions were more pronounced in meta-analyses with high between trial heterogeneity, in meta-analyses with large estimated treatment benefits, and in meta-analyses of complementary medicine. Restriction of meta-analyses to trials without exclusions resulted in smaller estimated treatment benefits, larger P values, and considerable decreases in between trial heterogeneity. CONCLUSION: Excluding patients from the analysis in randomised trials often results in biased estimates of treatment effects, but the extent and direction of bias is unpredictable. Results from intention to treat analyses should always be described in reports of randomised trials. In systematic reviews, the influence of exclusions from the analysis on estimated treatment effects should routinely be assessed.

Disagreements in meta-analyses using outcomes measured on continuous or rating scales: observer agreement study

OBJECTIVE: To study the inter-observer variation related to extraction of continuous and numerical rating scale data from trial reports for use in meta-analyses. DESIGN: Observer agreement study. DATA SOURCES: A random sample of 10 Cochrane reviews that presented a result as a standardised mean difference (SMD), the protocols for the reviews and the trial reports (n=45) were retrieved. DATA EXTRACTION: Five experienced methodologists and five PhD students independently extracted data from the trial reports for calculation of the first SMD result in each review. The observers did not have access to the reviews but to the protocols, where the relevant outcome was highlighted. The agreement was analysed at both trial and meta-analysis level, pairing the observers in all possible ways (45 pairs, yielding 2025 pairs of trials and 450 pairs of meta-analyses). Agreement was defined as SMDs that differed less than 0.1 in their point estimates or confidence intervals. RESULTS: The agreement was 53% at trial level and 31% at meta-analysis level. Including all pairs, the median disagreement was SMD=0.22 (interquartile range 0.07-0.61). The experts agreed somewhat more than the PhD students at trial level (61% v 46%), but not at meta-analysis level. Important reasons for disagreement were differences in selection of time points, scales, control groups, and type of calculations; whether to include a trial in the meta-analysis; and data extraction errors made by the observers. In 14 out of the 100 SMDs calculated at the meta-analysis level, individual observers reached different conclusions than the originally published review. CONCLUSIONS: Disagreements were common and often larger than the effect of commonly used treatments. Meta-analyses using SMDs are prone to observer variation and should be interpreted with caution. The reliability of meta-analyses might be improved by having more detailed review protocols, more than one observer, and statistical expertise.

A prediction model for personal radio frequency electromagnetic field exposure

Radio frequency electromagnetic fields (RF-EMF) in our daily life are caused by numerous sources such as fixed site transmitters (e.g. mobile phone base stations) or indoor devices (e.g. cordless phones). The objective of this study was to develop a prediction model which can be used to predict mean RF-EMF exposure from different sources for a large study population in epidemiological research. We collected personal RF-EMF exposure measurements of 166 volunteers from Basel, Switzerland, by means of portable exposure meters, which were carried during one week. For a validation study we repeated exposure measurements of 31 study participants 21 weeks after the measurements of the first week on average. These second measurements were not used for the model development. We used two data sources as exposure predictors: 1) a questionnaire on potentially exposure relevant characteristics and behaviors and 2) modeled RF-EMF from fixed site transmitters (mobile phone base stations, broadcast transmitters) at the participants' place of residence using a geospatial propagation model. Relevant exposure predictors, which were identified by means of multiple regression analysis, were the modeled RF-EMF at the participants' home from the propagation model, housing characteristics, ownership of communication devices (wireless LAN, mobile and cordless phones) and behavioral aspects such as amount of time spent in public transports. The proportion of variance explained (R2) by the final model was 0.52. The analysis of the agreement between calculated and measured RF-EMF showed a sensitivity of 0.56 and a specificity of 0.95 (cut-off: 90th percentile). In the validation study, the sensitivity and specificity of the model were 0.67 and 0.96, respectively. We could demonstrate that it is feasible to model personal RF-EMF exposure. Most importantly, our validation study suggests that the model can be used to assess average exposure over several months.

A model of osteoporosis impact in Switzerland 2000-2020

The aim of our study was to develop a modeling framework suitable to quantify the incidence, absolute number and economic impact of osteoporosis-attributable hip, vertebral and distal forearm fractures, with a particular focus on change over time, and with application to the situation in Switzerland from 2000 to 2020. A Markov process model was developed and analyzed by Monte Carlo simulation. A demographic scenario provided by the Swiss Federal Statistical Office and various Swiss and international data sources were used as model inputs. Demographic and epidemiologic input parameters were reproduced correctly, confirming the internal validity of the model. The proportion of the Swiss population aged 50 years or over will rise from 33.3% in 2000 to 41.3% in 2020. At the total population level, osteoporosis-attributable incidence will rise from 1.16 to 1.54 per 1,000 person-years in the case of hip fracture, from 3.28 to 4.18 per 1,000 person-years in the case of radiographic vertebral fracture, and from 0.59 to 0.70 per 1,000 person-years in the case of distal forearm fracture. Osteoporosis-attributable hip fracture numbers will rise from 8,375 to 11,353, vertebral fracture numbers will rise from 23,584 to 30,883, and distal forearm fracture numbers will rise from 4,209 to 5,186. Population-level osteoporosis-related direct medical inpatient costs per year will rise from 713.4 million Swiss francs (CHF) to CHF946.2 million. These figures correspond to 1.6% and 2.2% of Swiss health care expenditures in 2000. The modeling framework described can be applied to a wide variety of settings. It can be used to assess the impact of new prevention, diagnostic and treatment strategies. In Switzerland incidences of osteoporotic hip, vertebral and distal forearm fracture will rise by 33%, 27%, and 19%, respectively, between 2000 and 2020, if current prevention and treatment patterns are maintained. Corresponding absolute fracture numbers will rise by 36%, 31%, and 23%. Related direct medical inpatient costs are predicted to increase by 33%; however, this estimate is subject to uncertainty due to limited availability of input data.

Synoptic Analysis of the New York March 1888 Blizzard

The meteorological circumstances that led to the Blizzard of March 1888 that hit New York are analysed in Version 2 of the “Twentieth Century Reanalysis” (20CR). The potential of this data set for studying historical extreme events has not yet been fully explored. A detailed analysis of 20CR data alongside other data sources (including historical instrumental data and weather maps) for historical extremes such as the March 1888 blizzard may give insights into the limitations of 20CR. We find that 20CR reproduces the circulation pattern as well as the temperature development very well. Regarding the absolute values of variables such as snow fall or minimum and maximum surface pressure, there is anunderestimation of the observed extremes, which may be due to the low spatial resolution of 20CR and the fact that only the ensemble mean is considered. Despite this drawback, the dataset allows us to gain new information due to its complete spatial and temporal coverage.

Antiplatelets versus Anticoagulants for the Treatment of Cervical Artery Dissection: Bayesian Meta-Analysis

OBJECTIVE To compare the effects of antiplatelets and anticoagulants on stroke and death in patients with acute cervical artery dissection. DESIGN Systematic review with Bayesian meta-analysis. DATA SOURCES The reviewers searched MEDLINE and EMBASE from inception to November 2012, checked reference lists, and contacted authors. STUDY SELECTION Studies were eligible if they were randomised, quasi-randomised or observational comparisons of antiplatelets and anticoagulants in patients with cervical artery dissection. DATA EXTRACTION Data were extracted by one reviewer and checked by another. Bayesian techniques were used to appropriately account for studies with scarce event data and imbalances in the size of comparison groups. DATA SYNTHESIS Thirty-seven studies (1991 patients) were included. We found no randomised trial. The primary analysis revealed a large treatment effect in favour of antiplatelets for preventing the primary composite outcome of ischaemic stroke, intracranial haemorrhage or death within the first 3 months after treatment initiation (relative risk 0.32, 95% credibility interval 0.12 to 0.63), while the degree of between-study heterogeneity was moderate (τ(2) = 0.18). In an analysis restricted to studies of higher methodological quality, the possible advantage of antiplatelets over anticoagulants was less obvious than in the main analysis (relative risk 0.73, 95% credibility interval 0.17 to 2.30). CONCLUSION In view of these results and the safety advantages, easier usage and lower cost of antiplatelets, we conclude that antiplatelets should be given precedence over anticoagulants as a first line treatment in patients with cervical artery dissection unless results of an adequately powered randomised trial suggest the opposite.

A chrysophyte stomatocyst-based reconstruction of cold-season air temperature from Alpine Lake Silvaplana (AD 1500–2003); methods and concepts for quantitative inferences

Relatively little is known about past cold-season temperature variability in high-Alpine regions because of a lack of natural cold-season temperature proxies as well as under-representation of high-altitude sites in meteorological, early-instrumental and documentary data sources. Recent studies have shown that chrysophyte stomatocysts, or simply cysts (sub-fossil algal remains of Chrysophyceae and Synurophyceae), are among the very few natural proxies that can be used to reconstruct cold-season temperatures. This study presents a quantitative, high-resolution (5-year), cold-season (Oct–May) temperature reconstruction based on sub-fossil chrysophyte stomatocysts in the annually laminated (varved) sediments of high-Alpine Lake Silvaplana, SE Switzerland (1,789 m a.s.l.), since AD 1500. We first explore the method used to translate an ecologically meaningful variable based on a biological proxy into a simple climate variable. A transfer function was applied to reconstruct the ‘date of spring mixing’ from cyst assemblages. Next, statistical regression models were tested to convert the reconstructed ‘dates of spring mixing’ into cold-season surface air temperatures with associated errors. The strengths and weaknesses of this approach are thoroughly tested. One much-debated, basic assumption for reconstructions (‘stationarity’), which states that only the environmental variable of interest has influenced cyst assemblages and the influence of confounding variables is negligible over time, is addressed in detail. Our inferences show that past cold-season air-temperature fluctuations were substantial and larger than those of other temperature reconstructions for Europe and the Alpine region. Interestingly, in this study, recent cold-season temperatures only just exceed those of previous, multi-decadal warm phases since AD 1500. These findings highlight the importance of local studies to assess natural climate variability at high altitudes.

Reporting completeness of abstracts of systematic reviews published in leading dental specialty journals

The aim of this study was to investigate the reporting completeness of systematic review (SR) abstracts in leading dental specialty journals. Electronic and supplementary hand searching were undertaken to identify SRs published in seven dental specialty journals and in the Cochrane Database of Systematic Reviews. Abstract reporting completeness was evaluated using a checklist derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (prisma) guidelines. Descriptive statistics followed by univariate and multivariate analyses were conducted. Two-hundred and eighteen SR abstracts were identified. Reporting of interventions (94%), objectives (96%), data sources (81%), eligibility criteria (77%), and conclusions (97%) was adequate in the majority of reviews. However, inadequate reporting of participants (18%), results (42%), effect size (14%), level of significance (60%), and trial registration (100%) was commonplace. The mean overall reporting score was 79.1% (95% CI, 77.6-80.6). Only journal of publication was a significant predictor of overall reporting, with inferior results for all journals relative to Cochrane reviews, with scores ranging from -4.3% (95% CI, -8.74 to 0.08) to -35.6% (95% CI, -42.0 to -24.3) for the International Journal of Prosthodontics and the British Journal of Oral and Maxillofacial Surgery, respectively. Improved reporting of dental SR abstracts is needed and should be encouraged, as these abstracts may underpin influential clinical decisions.

The 1872 Baltic Sea storm surge

On 13 November 1872, the Baltic Sea coast from Denmark to Pomerania was devastated by an extreme storm surge caused by high winds. This is still the strongest surge on record, and understanding its development can contribute to improved risk assessment and protection. In this paper we trace this event in sea-level pressure and wind data from the “Twentieth Century Reanalysis” (20CR) and compare the results with other observation-based data sources. The analysis shows that, in the ensemble mean of 20CR, the general development is qualitatively well depicted, but with much reduced strength compared to other data sets. The same is true when selecting the ensemble member with maximum wind speeds.

Effect of psychological interventions on depressive symptoms in long-term rehabilitation after an acquired brain injury: a systematic review and meta-analysis

OBJECTIVE To summarize empirical studies on the effectiveness of psychological interventions in long-term rehabilitation after an acquired brain injury (ABI) in reducing depressive symptoms. DATA SOURCES A systematic literature search was conducted on MEDLINE, PsycINFO, Embase, and CINAHL to identify articles published between January 1990 and October 2011. Search terms included the 3 concepts (1) "brain injur*" or "stroke," (2) "psychotherap*" or "therapy" or "intervention" or "rehabilitation," and (3) "depress*." STUDY SELECTION Studies evaluating psychological interventions in patients after ABI were included. Time since injury was on average more than 1 year. Trials reported data on validated depression questionnaires before and after the psychological intervention. DATA EXTRACTION Two independent reviewers extracted information from the sample, the intervention, and the outcome of the included studies and calculated effect sizes (ESs) from depression questionnaires. Thirteen studies were included in a pre-post analysis. Seven studies were eligible for a meta-analysis of ESs in active interventions and control conditions. DATA SYNTHESIS Pre-post ESs were significant in 4 of 13 studies. The overall ES of .69 (95% confidence interval [CI], .29-1.09) suggests a medium effectiveness of psychological interventions on depressive symptoms compared with control conditions. Moderator analysis of the number of sessions and adequate randomization procedure did not show significant ES differences between strata. Studies with adequate randomization did not, however, suggest the effectiveness of psychological interventions on depressive symptoms after ABI. CONCLUSIONS Psychological interventions are a promising treatment option for depressive symptoms in long-term rehabilitation after ABI. Since only a few adequately randomized controlled trials (RCTs) exist, more RCTs are required to confirm this initial finding.

Epoetin and Darbepoetin for Managing Anemia in Patients Undergoing Cancer Treatment: Comparative Effectiveness Update

Objectives: To update the 2006 systematic review of the comparative benefits and harms of erythropoiesis-stimulating agent (ESA) strategies and non-ESA strategies to manage anemia in patients undergoing chemotherapy and/or radiation for malignancy (excluding myelodysplastic syndrome and acute leukemia), including the impact of alternative thresholds for initiating treatment and optimal duration of therapy. Data sources: Literature searches were updated in electronic databases (n=3), conference proceedings (n=3), and Food and Drug Administration transcripts. Multiple sources (n=13) were searched for potential gray literature. A primary source for current survival evidence was a recently published individual patient data meta-analysis. In that meta-analysis, patient data were obtained from investigators for studies enrolling more than 50 patients per arm. Because those data constitute the most currently available data for this update, as well as the source for on-study (active treatment) mortality data, we limited inclusion in the current report to studies enrolling more than 50 patients per arm to avoid potential differential endpoint ascertainment in smaller studies. Review methods: Title and abstract screening was performed by one or two (to resolve uncertainty) reviewers; potentially included publications were reviewed in full text. Two or three (to resolve disagreements) reviewers assessed trial quality. Results were independently verified and pooled for outcomes of interest. The balance of benefits and harms was examined in a decision model. Results: We evaluated evidence from 5 trials directly comparing darbepoetin with epoetin, 41 trials comparing epoetin with control, and 8 trials comparing darbepoetin with control; 5 trials evaluated early versus late (delay until Hb ≤9 to 11 g/dL) treatment. Trials varied according to duration, tumor types, cancer therapy, trial quality, iron supplementation, baseline hemoglobin, ESA dosing frequency (and therefore amount per dose), and dose escalation. ESAs decreased the risk of transfusion (pooled relative risk [RR], 0.58; 95% confidence interval [CI], 0.53 to 0.64; I2 = 51%; 38 trials) without evidence of meaningful difference between epoetin and darbepoetin. Thromboembolic event rates were higher in ESA-treated patients (pooled RR, 1.51; 95% CI, 1.30 to 1.74; I2 = 0%; 37 trials) without difference between epoetin and darbepoetin. In 14 trials reporting the Functional Assessment of Cancer Therapy (FACT)-Fatigue subscale, the most common patient-reported outcome, scores decreased by −0.6 in control arms (95% CI, −6.4 to 5.2; I2 = 0%) and increased by 2.1 in ESA arms (95% CI, −3.9 to 8.1; I2 = 0%). There were fewer thromboembolic and on-study mortality adverse events when ESA treatment was delayed until baseline Hb was less than 10 g/dL, in keeping with current treatment practice, but the difference in effect from early treatment was not significant, and the evidence was limited and insufficient for conclusions. No evidence informed optimal duration of therapy. Mortality was increased during the on-study period (pooled hazard ratio [HR], 1.17; 95% CI, 1.04 to 1.31; I2 = 0%; 37 trials). There was one additional death for every 59 treated patients when the control arm on-study mortality was 10 percent and one additional death for every 588 treated patients when the control-arm on-study mortality was 1 percent. A cohort decision model yielded a consistent result—greater loss of life-years when control arm on-study mortality was higher. There was no discernible increase in mortality with ESA use over the longest available followup (pooled HR, 1.04; 95% CI, 0.99 to 1.10; I2 = 38%; 44 trials), but many trials did not include an overall survival endpoint and potential time-dependent confounding was not considered. Conclusions: Results of this update were consistent with the 2006 review. ESAs reduced the need for transfusions and increased the risk of thromboembolism. FACT-Fatigue scores were better with ESA use but the magnitude was less than the minimal clinically important difference. An increase in mortality accompanied the use of ESAs. An important unanswered question is whether dosing practices and overall ESA exposure might influence harms.

Pleomorphic adenoma of the parotid: formal parotidectomy or limited surgery?

BACKGROUND Optimal surgery for pleomorphic adenoma of the parotid is controversial. In the present review, we discuss the advantages and disadvantages of the various approaches after addressing the surgical pathology of the parotid pleomorphic adenoma capsule and its influence on surgery. DATA SOURCES PubMed literature searches were performed to identify original studies. CONCLUSIONS Almost all pleomorphic adenomas can be effectively treated by formal parotidectomy, but the procedure is not mandatory. Extracapsular dissection is a minimal margin surgery; therefore, in the hands of a novice or occasional parotid surgeon, it may result in higher rates of recurrence. Partial superficial parotidectomy may be a good compromise. The tumor is removed with a greater cuff of healthy parotid tissue than in extracapsular dissection. This may minimize the recurrence rate. On the other hand, the removal of healthy parotid tissue compared with formal parotidectomy is limited, thus minimizing complications such as facial nerve dysfunction and Frey syndrome.

Assessing and mapping LD and SLM to directly support the planning and scaling up of SLM interventions to combat desertification

Global investment in Sustainable Land Management (SLM) has been substantial, but knowledge gaps remain. Overviews of where land degradation (LD) is taking place and how land users are addressing the problem using SLM are still lacking for most individual countries and regions. Relevant maps focus more on LD than SLM, and they have been compiled using different methods. This makes it impossible to compare the benefits of SLM interventions and prevents informed decision-making on how best to invest in land. To fill this knowledge gap, a standardised mapping method has been collaboratively developed by the World Overview of Conservation Approaches and Technologies (WOCAT), FAO’s Land Degradation Assessment in Drylands (LADA) project, and the EU’s Mitigating Desertification and Remediating Degraded Land (DESIRE) project. The method generates information on the distribution and characteristics of LD and SLM activities and can be applied at the village, national, or regional level. It is based on participatory expert assessment, documents, and surveys. These data sources are spatially displayed across a land-use systems base map. By enabling mapping of the DPSIR framework (Driving Forces-Pressures-State-Impacts-Responses) for degradation and conservation, the method provides key information for decision-making. It may also be used to monitor LD and conservation following project implementation. This contribution explains the mapping method, highlighting findings made at different levels (national and local) in South Africa and the Mediterranean region. Keywords: Mapping, Decision Support, Land Degradation, Sustainable Land Management, Ecosystem Services, Participatory Expert Assessment

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Design Systematic review and network meta-analysis using Bayesian statistics. Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate. Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome. Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy. Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.