Background
Advance care planning is widely advocated to improve outcomes in end-of-life care for patients suffering from heart failure. But until now, there has been no systematic evaluation of the ...impact of advance care planning (ACP) on clinical outcomes. Our aim was to determine the effect of ACP in heart failure through a meta-analysis of randomized controlled trials (RCTs).
Methods
We searched CINAHL, Cochrane Central Register of Controlled Trials, Database of Systematic Reviews, Embase, ERIC, Ovid MEDLINE, Science Citation Index and PsycINFO (inception to July 2018). We selected RCTs including adult patients with heart failure treated in a hospital, hospice or community setting. Three reviewers independently screened studies, extracted data, assessed the risk of bias (Cochrane risk of bias tool) and evaluated the quality of evidence (GRADE tool) and analysed interventions according to the Template for Intervention Description and Replication (TIDieR). We calculated standardized mean differences (SMD) in random effects models for pooled effects using the generic inverse variance method.
Results
Fourteen RCTs including 2924 participants met all of the inclusion criteria. There was a moderate effect in favour of ACP for quality of life (SMD, 0.38; 95% CI 0.09 to 0.68), patients’ satisfaction with end-of-life care (SMD, 0.39; 95% CI 0.14 to 0.64) and the quality of end-of-life communication (SMD, 0.29; 95% CI 0.17 to 0.42) for patients suffering from heart failure. ACP seemed most effective if it was introduced at significant milestones in a patient’s disease trajectory, included family members, involved follow-up appointments and considered ethnic preferences. Several sensitivity analyses confirmed the statistically significant direction of effect. Heterogeneity was mainly due to different study settings, length of follow-up periods and compositions of ACP.
Conclusions
ACP improved quality of life, patient satisfaction with end-of-life care and the quality of end-of-life communication for patients suffering from heart failure and could be most effective when the right timing, follow-up and involvement of important others was considered.
Randomization, allocation concealment, and blind outcome assessment have been shown to reduce bias in human studies. Authors from the Collaborative Approach to Meta Analysis and Review of Animal Data ...from Experimental Studies (CAMARADES) collaboration recently found that these features protect against bias in animal stroke studies. We extended the scope the work from CAMARADES to include investigations of treatments for any condition.
We conducted an overview of systematic reviews. We searched Medline and Embase for systematic reviews of animal studies testing any intervention (against any control) and we included any disease area and outcome. We included reviews comparing randomized versus not randomized (but otherwise controlled), concealed versus unconcealed treatment allocation, or blinded versus unblinded outcome assessment.
Thirty-one systematic reviews met our inclusion criteria: 20 investigated treatments for experimental stroke, 4 reviews investigated treatments for spinal cord diseases, while 1 review each investigated treatments for bone cancer, intracerebral hemorrhage, glioma, multiple sclerosis, Parkinson's disease, and treatments used in emergency medicine. In our sample 29% of studies reported randomization, 15% of studies reported allocation concealment, and 35% of studies reported blinded outcome assessment. We pooled the results in a meta-analysis, and in our primary analysis found that failure to randomize significantly increased effect sizes, whereas allocation concealment and blinding did not. In our secondary analyses we found that randomization, allocation concealment, and blinding reduced effect sizes, especially where outcomes were subjective.
Our study demonstrates the need for randomization, allocation concealment, and blind outcome assessment in animal research across a wide range of outcomes and disease areas. Since human studies are often justified based on results from animal studies, our results suggest that unduly biased animal studies should not be allowed to constitute part of the rationale for human trials.
To evaluate the diagnostic accuracy of a single CEA (carcinoembryonic antigen) blood test in detecting colorectal cancer recurrence.
Patients who have undergone curative resection for primary ...colorectal cancer are typically followed up with scheduled CEA testing for 5 years. Decisions to investigate further (usually by CT imaging) are based on single test results, reflecting international guidelines.
A secondary analysis was undertaken of data from the FACS trial (two arms included CEA testing). The composite reference standard applied included CT-CAP imaging, clinical assessment and colonoscopy. Accuracy in detecting recurrence was evaluated in terms of sensitivity, specificity, likelihood ratios, predictive values, time-dependent area under the ROC curves, and operational performance when used prospectively in clinical practice are reported.
Of 582 patients, 104 (17.9%) developed recurrence during the 5 year follow-up period. Applying the recommended threshold of 5μg/L achieves at best 50.0% sensitivity (95% CI: 40.1-59.9%); in prospective use in clinical practice it would lead to 56 missed recurrences (53.8%; 95% CI: 44.2-64.4%) and 89 false alarms (56.7% of 157 patients referred for investigation). Applying a lower threshold of 2.5μg/L would reduce the number of missed recurrences to 36.5% (95% CI: 26.5-46.5%) but would increase the false alarms to 84.2% (924/1097 referred). Some patients are more prone to false alarms than others-at the 5μg/L threshold, the 89 episodes of unnecessary investigation were clustered in 29 individuals.
Our results demonstrated very low sensitivity for CEA, bringing to question whether it could ever be used as an independent triage test. It is not feasible to improve the diagnostic performance of a single test result by reducing the recommended action threshold because of the workload and false alarms generated. Current national and international guidelines merit re-evaluation and options to improve performance, such as making clinical decisions on the basis of CEA trend, should be further assessed.
Hypertension is a leading cause of cardiovascular disease, which is the cause of one-third of global deaths and is a primary and rising contributor to the global disease burden. The objective of this ...systematic review was to determine the prevalence and awareness of hypertension among the inhabitants of Tibet and its association with altitude, using the data from published observational studies.
We conducted electronic searches in Medline, Embase, ISI Web of Science and Global Health. No gender or language restrictions were imposed. We assessed the methodological characteristics of included studies using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria. Two reviewers independently determined the eligibility of studies, assessed the methodology of included studies and extracted the data. We used meta-regression to estimate the degree of change in hypertension prevalence with increasing altitude.
We identified 22 eligible articles of which eight cross-sectional studies with a total of 16 913 participants were included. The prevalence of hypertension ranged between 23% and 56%. A scatter plot of altitude against overall prevalence revealed a statistically significant correlation (r=0.68; p=0.04). Meta-regression analysis revealed a 2% increase in the prevalence of hypertension with every 100 m increase in altitude (p=0.06). The locations and socioeconomic status of subjects affected the awareness and subsequent treatment and control of hypertension.
The results from cross-sectional studies suggest that there is a significant correlation between altitude and the prevalence of hypertension among inhabitants of Tibet. The socioeconomic status of the inhabitants can influence awareness and management of hypertension. Very little research into hypertension has been conducted in other prefectures of Tibet where the altitude is much higher. Further research examining the impact of altitude on blood pressure is warranted.
Placebos are widely used in clinical practice in spite of ethical restrictions. Whether such use is justified depends in part on the relative benefit of placebos compared to 'active' treatments. A ...direct test for differences between placebo and 'active' treatment effects has not been conducted.
We aimed to test for differences between treatment and placebo effects within similar trial populations.
A Cochrane Review compared placebos with no treatment in three-armed trials (no treatment, placebo, and treatment). We added an analysis of treatment and placebo differences within the same trials. SYNTHESIS METHODS: For continuous outcomes we compared mean differences between placebo and no treatment with mean differences between treatment and placebo. For binary outcomes we compared the risk ratio for treatment benefit (versus placebo) with the risk ratio for placebo benefit (versus no treatment). We conducted several preplanned subgroup analyses: objective versus subjective outcomes, conditions tested in three or more trials, and trials with varying degrees of bias.
In trials with continuous outcomes (n = 115) we found no difference between treatment and placebo effects (MD = -0.29, 95% CI -0.62 to 0.05, P = 0.10). In trials with binary outcomes (n = 37) treatments were significantly more effective than placebos (RRR = 0.72, 95%CI = 0.61 to 0.86, P = 0.0003). Treatment and placebo effects were not different in 22 out of 28 predefined subgroup analyses. Of the six subgroups with differences treatments were more effective than placebos in five. However when all criteria for reducing bias were ruled out (continuous outcomes) placebos were more effective than treatments (MD = 1.59, 95% CI = 0.40 to 2.77, P = 0.009).
Placebos and treatments often have similar effect sizes. Placebos with comparatively powerful effects can benefit patients either alone or as part of a therapeutic regime, and trials involving such placebos must be adequately blinded.
Irritable Bowel Syndrome (IBS) is a common chronic gastrointestinal disorder and the evidence for efficacy of most drug therapies in the treatment of IBS is weak. A popular alternative is probiotics, ...which have been used in several conditions. including IBS. Probiotics are live microbial food supplements.The aim of this systematic review and meta-analysis of randomized trials study was to evaluate the efficacy of probiotics in alleviating symptoms in patients with irritable bowel syndrome. We searched Ovid versions of MEDLINE (1950-2007), EMBASE (1980-2007), CINAHL (1982-2007), AMED (1985-2007), the Cochrane library and hand searched retrieved papers.
We identified 14 randomized placebo controlled trials. Combined data suggested a modest improvement in overall symptoms after several weeks of treatment: for dichotomous data from seven trials the overall Odds Ratio (OR) was 1.6 (95% CI, 1.2 to 2.2); for continuous data from six trials the standardised mean difference (SMD) was 0.23 (95% CI, 0.07 to 0.38).For individual symptoms the results differed between the pooled dichotomous and pooled continuous data. Trials varied in relation to the length of treatment (4-26 weeks), dose, organisms and strengths of probiotics used.
Probiotics may have a role in alleviating some of the symptoms of IBS, a condition for which currently evidence of efficacy of drug therapies is weak. However, as IBS is a condition that is chronic and usually intermittent longer term trials are recommended. Such research should focus on the type, optimal dose of probiotics and the subgroups of patients who are likely to benefit the most.
The optimal time for initiation of dialysis and which modality to choose as the starting therapy is currently unclear. This systematic review aimed to assess the recommendations across high-quality ...clinical practice guidelines (CPGs) related to the start of dialysis.
We systematically searched MEDLINE, EMBASE, Web of Science, LILACS, and databases of organisations that develop CPGs between September 2008 to August 2021 for CPGs that addressed recommendations on the timing of initiation of dialysis, selection of dialysis modality, and interventions to support the decision-making process to select a dialysis modality. We used the Appraisal of Guidelines for Research and Evaluation instrument to assess the methodological quality of the CPGs and included only high-quality CPGs. This study is registered in PROSPERO, number CRD42018110325.
We included 12 high-quality CPGs. Six CPGs addressed recommendations related to the timing of initiating dialysis, and all agreed on starting dialysis in the presence of symptoms or signs. Six CPGs addressed recommendations related to the selection of modality but varied greatly in their content. Nine CPGs addressed recommendations related to interventions to support the decision-making process. Eight CPGs agreed on recommended educational programs that include information about dialysis options. One CPG considered using patient decision aids a strong recommendation.
We could have missed potentially relevant guidelines since we limited our search to CPGs published from 2008, and we set up a cut-off point of 60% in domains of the rigour of development and editorial independence.
High-quality CPGs related to the process of starting dialysis were consistent in initiating dialysis in the presence of symptoms or signs and offering patients education at the point of decision-making. There was variability in how CPGs addressed the issue of dialysis modality selection. CPGs should improve strategies on putting recommendations into practice and the quality of evidence to aid decision-making for patients.
The protocol of this systematic review has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD CRD42018110325. https://clinicaltrials.gov/ct2/show/CRD42018110325.
Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test ...data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer. We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve greater than or equal to 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors. Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.
Meningococcal disease is a rapidly progressive childhood infection of global importance. To our knowledge, no systematic quantitative research exists into the occurrence of symptoms before admission ...to hospital.
Data were obtained from questionnaires answered by parents and from primary-care records for the course of illness before admission to hospital in 448 children (103 fatal, 345 non-fatal), aged 16 years or younger, with meningococcal disease. In 373 cases, diagnosis was confirmed with microbiological techniques. The rest of the children were included because they had a purpuric rash, and either meningitis or evidence of septicaemic shock. Results were standardised to UK case-fatality rates.
The time-window for clinical diagnosis was narrow. Most children had only non-specific symptoms in the first 4–6 h, but were close to death by 24 h. Only 165 (51%) children were sent to hospital after the first consultation. The classic features of haemorrhagic rash, meningism, and impaired consciousness developed late (median onset 13–22 h). By contrast, 72% of children had early symptoms of sepsis (leg pains, cold hands and feet, abnormal skin colour) that first developed at a median time of 8 h, much earlier than the median time to hospital admission of 19 h.
Classic clinical features of meningococcal disease appear late in the illness. Recognising early symptoms of sepsis could increase the proportion of children identified by primary-care clinicians and shorten the time to hospital admission. The framework within which meningococcal disease is diagnosed should be changed to emphasise identification of these early symptoms by parents and clinicians.
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