Global, regional and national incidence and causes of needlestick injuries: a systematic review and meta-analysi

Background: Needlestick injuries (NSIs) are one of the most serious occupational hazards for healthcare workers (HCWs). Aims: The aim of this study was to evaluate the incidence and causes of NSIs globally. Methods: A systematic review and meta-analysis of data from January 2000 to May 2020 collected from Scopus, PubMed, Embase, Web of Science, and Google Scholar. The Newcastle–Ottawa Scale was used to assess the quality of the included articles. The data obtained were analysed by R version 3/5/0, and 113 articles were retrieved. Results: There were 113 studies with a total of 525 798 HCWs. The incidence of NSIs was 43%. Africa had the highest rate of these injuries of 51%, and the World Health Organization (WHO) African Region had the highest incidence among WHO regions of 52%. Women were more frequently affected by NSIs than men. Hepatitis C virus infection was the disease most commonly transmitted via NSIs (21%). The highest rates of NSIs according to causes, devices, hospital locations, occupations and procedures were for recapping of needles, needles, general wards, nurses and waste disposal, respectively. Conclusion: The incidence of NSIs is gradually decreasing. The findings of this study can contribute to improving the decision-making process for reducing NSIs in HCWs.

Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers.

Production of short-chain fatty acids (SCFAs), especially butyrate, in the gut microbiome is required for optimal health but is frequently limited by the lack of fermentable fiber in the diet. We attempted to increase butyrate production by supplementing the diets of 174 healthy young adults for 2 weeks with resistant starch from potatoes (RPS), resistant starch from maize (RMS), inulin from chicory root, or an accessible corn starch control. RPS resulted in the greatest increase in total SCFAs, including butyrate. Although the majority of microbiomes responded to RPS with increases in the relative abundance of bifidobacteria, those that responded with an increase in Ruminococcus bromii or Clostridium chartatabidum were more likely to yield higher butyrate concentrations, especially when their microbiota were replete with populations of the butyrate-producing species Eubacterium rectale RMS and inulin induced different changes in fecal communities, but they did not generate significant increases in fecal butyrate levels.IMPORTANCE These results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual's microbiota in determining whether or not they respond to a specific dietary supplement. In particular, R. bromii or C. chartatabidum may be required for enhanced butyrate production in response to RS. Bifidobacteria, though proficient at degrading RS and inulin, may not contribute to the butyrogenic effect of those fermentable fibers in the short term.

Estrategia didáctica para la formación bioestadística del residente en la Atención Secundaria de Salud en Santiago de Cuba / Estratégia didática para o treinamento bioestatístico do residente na Atenção Secundária à Saúde em Santiago de Cuba / Didactic strategy for the biostatistical training of the resident in the Secondary Health Care in Santiago de Cuba

Introducción: la aplicación de la Bioestadística es imprescindible para el desarrollo de la función asistencial, docente, investigativa y administrativa del médico en especialización en el nivel de Atención Secundaria de Salud (ASS). Objetivo: exponer los fundamentos que sustentan el diseño y los resultados de la aplicación parcial de una estrategia didáctica para la formación bioestadística del residente en el nivel de Atención Secundaria de Salud. Método: se realizó un estudio pedagógico, prospectivo, que tiene como fundamento teórico el modelo de autoformación continua, asistida de la lógica estadística, mediante el empleo consecuente de la teoría holístico configuracional y el método holístico dialéctico. Para elaborar la estrategia se aplicó el método sistémico estructural y para validar sus resultados las técnicas de criterios de especialistas y la validación empírica. Resultados: se elaboró una estrategia didáctica para la formación bioestadística del residente en el nivel de ASS y se reveló sus fundamentos teóricos, estructura y las premisas y requerimiento para su implementación en la práctica pedagógica. Su aplicación posibilitó un salto cualitativamente superior en la elaboración por los residentes de sus respectivos de proyectos e informes finales de trabajo de terminación de la residencia (p≤0,05). Conclusiones: la aplicación de la estrategia didáctica para la formación Bioestadística del residente en el nivel de ASS posibilitó alcanzar resultados cualitativamente superiores en la formación Bioestadística del residente(AU)

Introduction: the application of Biostatistics is essential for the development of the assistance, teaching, research and administrative function of the physician specializing in the level of Secondary Health Care (ASS). Objective: to expose the fundamentals that support the design and the results of the partial application of a didactic strategy for the biostatistical training of the resident at the level of Secondary Health Care. Method: a prospective pedagogical study was carried out, whose theoretical basis is the continuous self-training model, assisted by statistical logic, through the consistent use of holistic configurational theory and the holistic dialectical method. The structural systemic method was applied to elaborate the strategy and to validate its results the techniques of specialists criteria and empirical validation. Results: a didactic strategy for the biostatistical training of the resident at the ASS level was developed and its theoretical foundations, structure and premises and requirement for its implementation in pedagogical practice were revealed. Its application enabled a qualitatively higher leap in the preparation by the residents of their respective projects and final reports of work of completion of the residence (p≤0.05). Conclusions: the application of the didactic strategy for the resident's Biostatistics training at the ASS level made it possible to achieve qualitatively superior results in the resident's Biostatistics training(AU)

Introdução: a aplicação da Bioestatística é essencial para o desenvolvimento da função assistencial, de ensino, de pesquisa e administrativa do médico especialista no nível da Atenção Secundária à Saúde (ASS). Objetivo: expor os fundamentos que sustentam o desenho e os resultados da aplicação parcial de uma estratégia didática para o treinamento bioestatístico do residente no nível da Atenção Secundária à Saúde. Método: foi realizado um estudo pedagógico prospectivo, cuja base teórica é o modelo de auto-treinamento contínuo, auxiliado pela lógica estatística, através do uso consistente da teoria configuracional holística e do método dialético holístico. O método sistêmico estrutural foi aplicado para elaborar a estratégia e validar seus resultados as técnicas de critérios de especialistas e validação empírica. Resultados: foi desenvolvida uma estratégia didática para a formação bioestatística do residente no nível ASS e foram revelados seus fundamentos teóricos, estrutura e premissas e requisitos para sua implementação na prática pedagógica. Sua aplicação permitiu um salto qualitativamente maior na preparação pelos moradores de seus respectivos projetos e relatórios finais do trabalho de conclusão da residência (p≤0,05). Conclusões: a aplicação da estratégia didática para o treinamento em Bioestatística do residente no nível ASS tornou possível alcançar resultados qualitativamente superiores no treinamento em Bioestatística do residente(AU)

Individual spindle detection and analysis in high-density recordings across the night and in thalamic stroke.

Sleep spindles are thalamocortical oscillations associated with several behavioural and clinical phenomena. In clinical populations, spindle activity has been shown to be reduced in schizophrenia, as well as after thalamic stroke. Automatic spindle detection algorithms present the only feasible way to systematically examine individual spindle characteristics. We took an established algorithm for spindle detection, and adapted it to high-density EEG sleep recordings. To illustrate the detection and analysis procedure, we examined how spindle characteristics changed across the night and introduced a linear mixed model approach applied to individual spindles in adults (n = 9). Next we examined spindle characteristics between a group of paramedian thalamic stroke patients (n = 9) and matched controls. We found a high spindle incidence rate and that, from early to late in the night, individual spindle power increased with the duration and globality of spindles; despite decreases in spindle incidence and peak-to-peak amplitude. In stroke patients, we found that only left-sided damage reduced individual spindle power. Furthermore, reduction was specific to posterior/fast spindles. Altogether, we demonstrate how state-of-the-art spindle detection techniques, applied to high-density recordings, and analysed using advanced statistical approaches can yield novel insights into how both normal and pathological circumstances affect sleep.

Time-to-Event Modeling of Left- or Right-Censored Toxicity Data in Nonclinical Drug Toxicology.

A time-to-event (TTE) model has been developed to characterize a histopathology toxicity that can only be detected at the time of animal sacrifice. The model of choice was a hazard model with a Weibull distribution and dose was a significant covariate. The diagnostic plots showed a satisfactory fit of the data, despite the high degree of left and right censoring. Comparison to a probabilistic logit model shows similar performance in describing the data with a slight underestimation of survival by the Logit model. However, the TTE model was found to be more predictive in extrapolating toxicity risk beyond the observation range of a truncated dataset. The diagnostic and comparison outcomes would suggest using the TTE approach as a first choice for characterizing short and long-term risk from nonclinical toxicity studies. However, further investigations are needed to explore the domain of application of this kind of approach in drug safety assessment.

Efficient treatment allocation in 2 × 2 multicenter trials when costs and variances are heterogeneous.

At the design stage of a study, it is crucial to compute the sample size needed for treatment effect estimation with maximum precision and power. The optimal design depends on the costs, which may be known at the design stage, and on the outcome variances, which are unknown. A balanced design, optimal for homogeneous costs and variances, is typically used. An alternative to the balanced design is a design optimal for the known and possibly heterogeneous costs, and homogeneous variances, called costs considering design. Both designs suffer from loss of efficiency, compared with optimal designs for heterogeneous costs and variances. For 2 × 2 multicenter trials, we compute the relative efficiency of the balanced and the costs considering designs, relative to the optimal designs. We consider 2 heterogeneous costs and variance scenarios (in 1 scenario, 2 treatment conditions have small and 2 have large costs and variances; in the other scenario, 1 treatment condition has small, 2 have intermediate, and 1 has large costs and variances). Within these scenarios, we examine the relative efficiency of the balanced design and of the costs considering design as a function of the extents of heterogeneity of the costs and of the variances and of their congruence (congruent when the cheapest treatment has the smallest variance, incongruent when the cheapest treatment has the largest variance). We find that the costs considering design is generally more efficient than the balanced design, and we illustrate this theory on a 2 × 2 multicenter trial on lifestyle improvement of patients in general practices.

Bayesian hierarchical model for analyzing multiresponse longitudinal pharmacokinetic data.

Traditional Chinese medicine (TCM) is a very complex mixture containing many different ingredients. Thus, statistical analysis of traditional Chinese medicine data becomes challenging, as one needs to handle the association among the observed data across different time points and across different ingredients of the multivariate response. This paper builds a 3-stage Bayesian hierarchical model for analyzing multivariate response pharmacokinetic data. Usually, the dimensionality of the parameter space is very huge, which leads to the parameter-estimation difficulty. So we take the hybrid Markov chain Monte Carlo algorithms to obtain the posterior Bayesian estimation of corresponding parameters in our model. Both simulation study and real-data analysis show that our theoretical model and Markov chain Monte Carlo algorithms perform well, and especially the correlation among different ingredients can be calculated very accurately.

Subgroup finding via Bayesian additive regression trees.

We provide a Bayesian decision theoretic approach to finding subgroups that have elevated treatment effects. Our approach separates the modeling of the response variable from the task of subgroup finding and allows a flexible modeling of the response variable irrespective of potential subgroups of interest. We use Bayesian additive regression trees to model the response variable and use a utility function defined in terms of a candidate subgroup and the predicted response for that subgroup. Subgroups are identified by maximizing the expected utility where the expectation is taken with respect to the posterior predictive distribution of the response, and the maximization is carried out over an a priori specified set of candidate subgroups. Our approach allows subgroups based on both quantitative and categorical covariates. We illustrate the approach using simulated data set study and a real data set. Copyright © 2017 John Wiley & Sons, Ltd.

Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Department of Medicine; Department of Biostatistics and Computational Biology; Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; Johns Hopkins University, Baltimore; University of Wisconsin Carbone Cancer Center; School of Medicine and Public Health; Madison; Fox Chase Cancer Center, Temple University Health System, Philadelphia; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis; Mayo Clinic, Rochester, MN; University Hospitals Case Medical Center, Seidman Cancer Center; Cleveland Clinic Taussig Cancer Institute; Both in Cleveland; University of Virginia Cancer Center, Charlottesville; Comprehensive Cancer Centers of Nevada, Las Vegas; Siteman Cancer Center, Washington University School of Medicine, St. Louis; NorthShore University Health System, Evanston, IL; University of Michigan Comprehensive Cancer Center, Ann Arbor; Rutgers Cancer Institute of New Jersey, New Brunswick.N Engl J Med. 2015 Aug 20;373(8):737-46. [Epub 2015 Aug 5]. doi: 10.1056/NEJMoa1503747.

BACKGROUND: Androgen deprivation therapy (ADT) has been the backbone of treatment for metastatic prostate cancer since the 1940s. We assessed whether concomitant treatment with ADT plus docetaxel would result in longer overall survival than that with ADT alone. METHODS: We assigned men with metastatic, hormone-sensitive prostate cancer to receive either ADT plus docetaxel (at a dose of 75mg per square meter of body-surface area every 3wk for 6 cycles) or ADT alone. The primary objective was to test the hypothesis that the median overall survival would be 33.3% longer among patients receiving docetaxel added to ADT early during therapy than among patients receiving ADT alone. RESULTS: A total of 790 patients (median age, 63y) underwent randomization. After a median follow-up of 28.9 months, the median overall survival was 13.6 months longer with ADT plus docetaxel (combination therapy) than with ADT alone (57.6 vs. 44.0mo; hazard ratio for death in the combination group, 0.61; 95% confidence interval [CI]: 0.47-0.80; P<0.001). The median time to biochemical, symptomatic, or radiographic progression was 20.2 months in the combination group, as compared with 11.7 months in the ADT-alone group (hazard ratio, 0.61; 95% CI: 0.51-0.72; P<0.001). The rate of a prostate-specific antigen level of less than 0.2ng/ml at 12 months was 27.7% in the combination group vs. 16.8% in the ADT-alone group (P<0.001). In the combination group, the rate of grade 3 or 4 febrile neutropenia was 6.2%, the rate of grade 3 or 4 infection with neutropenia was 2.3%, and the rate of grade 3 sensory neuropathy and of grade 3 motor neuropathy was 0.5%. CONCLUSIONS: Six cycles of docetaxel at the beginning of ADT for metastatic prostate cancer resulted in significantly longer overall survival than that with ADT alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00309985.).

Detecting time-specific differences between temporal nonlinear curves: Analyzing data from the visual world paradigm.

In multiple fields of study, time series measured at high frequencies are used to estimate population curves that describe the temporal evolution of some characteristic of interest. These curves are typically nonlinear, and the deviations of each series from the corresponding curve are highly autocorrelated. In this scenario, we propose a procedure to compare the response curves for different groups at specific points in time. The method involves fitting the curves, performing potentially hundreds of serially correlated tests, and appropriately adjusting the overall alpha level of the tests. Our motivating application comes from psycholinguistics and the visual world paradigm. We describe how the proposed technique can be adapted to compare fixation curves within subjects as well as between groups. Our results lead to conclusions beyond the scope of previous analyses.

Estimating the average treatment effects of nutritional label use using subclassification with regression adjustment.

Propensity score methods are common for estimating a binary treatment effect when treatment assignment is not randomized. When exposure is measured on an ordinal scale (i.e. low-medium-high), however, propensity score inference requires extensions which have received limited attention. Estimands of possible interest with an ordinal exposure are the average treatment effects between each pair of exposure levels. Using these estimands, it is possible to determine an optimal exposure level. Traditional methods, including dichotomization of the exposure or a series of binary propensity score comparisons across exposure pairs, are generally inadequate for identification of optimal levels. We combine subclassification with regression adjustment to estimate transitive, unbiased average causal effects across an ordered exposure, and apply our method on the 2005-2006 National Health and Nutrition Examination Survey to estimate the effects of nutritional label use on body mass index.

Bayesian estimation in random effects meta-analysis using a non-informative prior.

Pooling information from multiple, independent studies (meta-analysis) adds great value to medical research. Random effects models are widely used for this purpose. However, there are many different ways of estimating model parameters, and the choice of estimation procedure may be influential upon the conclusions of the meta-analysis. In this paper, we describe a recently proposed Bayesian estimation procedure and compare it with a profile likelihood method and with the DerSimonian-Laird and Mandel-Paule estimators including the Knapp-Hartung correction. The Bayesian procedure uses a non-informative prior for the overall mean and the between-study standard deviation that is determined by the Berger and Bernardo reference prior principle. The comparison of these procedures focuses on the frequentist properties of interval estimates for the overall mean. The results of our simulation study reveal that the Bayesian approach is a promising alternative producing more accurate interval estimates than those three conventional procedures for meta-analysis. The Bayesian procedure is also illustrated using three examples of meta-analysis involving real data. Copyright © 2016 John Wiley & Sons, Ltd.

Down syndrome screening information in midwifery practices in the Netherlands: Strategies to integrate biomedical information.

The aim of this qualitative study was to analyse counselling with regard to prenatal screening in midwifery consultations in the Netherlands where a national prenatal screening programme has only existed since 2007, after years of social and political debates. The methodology is based on in situ observations of 25 counselling consultations in four midwifery practices in two main cities in the Netherlands. The results of this study show that, since midwives are obliged to offer information on Down syndrome screening to all pregnant women (2007), they have to deal with the communication of medical screening information using biostatistical concepts to explain risks, calculations, probabilities and chromosomal anomalies. In order to avoid the risk of medicalization of their consultation, midwives develop strategies that allow them to integrate this new biomedical discourse while maintaining their low medicalized approach of midwife-led care. One of their main strategies is to switch from 'alarming' biomedical messages to 'reassuring words' in order to manage the anxiety induced by the information and to keep the control over their low medicalized consultation. They also tend to distance themselves from the obligation to talk about screening. The way midwives handle these counselling consultations allows them to respect their obligation to propose information, and to remain faithful to their struggle to protect the natural process of pregnancy as well as their professional autonomy.

Capabilities and the Definition of Health: Comments on Venkatapuram.

Sridhar Venkatapuram's Health Justice argues that health is a 'metacapability' - specifically, as the metacapability of having the ten 'central human capabilities' described by Martha Nussbaum. This cannot be right, as it provides no basis for distinguishing health from education, riches, or love. An amendment correcting this problem is suggested, namely that health is the involuntary, bodily aspect of the metacapability for the central capabilities. This amendment is defended against the objection that it fails to capture some important aspects of mental health.

Growth reconstitution following antiretroviral therapy and nutritional supplementation: systematic review and meta-analysis.

OBJECTIVE: As antiretroviral therapy (ART) expands for HIV-infected children, it is important to determine its impact on growth. We quantified growth and its determinants following ART in resource-limited (RLS) and developed settings. DESIGN: Systematic review and meta-analysis. METHODS: We searched publications reporting growth [weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z scores] in HIV-infected children following ART through August 2014. Inclusion criteria were as follows: younger than 18 years; ART; at least 20 patients; growth at ART; and post-ART growth. Standardized and overall weighted mean differences were calculated using random-effects models. RESULTS: A total of 67 articles were eligible (RLS = 54; developed settings = 13). Mean age was 5.8 years, and comparable between settings (P = 0.90). Baseline growth was substantially lower in RLS vs. developed settings (WAZ -2.1 vs. -0.5; HAZ -2.2 vs. -0.9; both P < 0.01). Rate of weight but not height reconstitution during 12 and 24 months was higher in RLS (12-month WAZ change 0.84 vs. 0.17, P < 0.01). Growth deficits persisted in RLS after 2 years ART (P = 0.04). Younger cohort age was associated with greater growth reconstitution. Protease inhibitor and nonnucleoside reverse-transcriptase inhibitor regimens yielded comparable growth. Adjusting for age and setting, cohorts with nutritional supplements had greater growth gains (24-month rate difference: WAZ 0.55, P = 0.03; HAZ 0.60, P = 0.007). Supplement benefits were attenuated after adjusting for baseline cohort growth. CONCLUSION: RLS children had substantial growth deficits compared with developed settings counterparts at ART; growth shortfalls in RLS persisted despite reconstitution. Earlier age and nutritional supplementation at ART may improve growth outcomes. Scant data on supplementation limit evaluation of impact and underscores need for systematic data collection regarding supplementation in pediatric ART programmes/cohorts.

The Czech Surveillance System for Invasive Pneumococcal Disease, 2008-2013: A Follow-Up Assessment and Sensitivity Estimation.

BACKGROUND: Invasive pneumococcal disease (IPD) is caused by Streptococcus pneumoniae and mostly presents as pneumonia, sepsis or meningitis. A notable portion of IPD cases is vaccine preventable and the pneumococcal conjugate vaccine (PCV) was introduced into the routine childhood immunization programs in many countries during the last decades. OBJECTIVES: Before PCV introduction in the Czech Republic in 2010, a national surveillance system for IPD was implemented in 2008 and further improved in 2011. In this study, we describe the new surveillance system for the first time and measure its sensitivity between 2010 and 2013 using the capture-recapture method. Furthermore, we describe the recent epidemiological trend of IPD, taking sensitivity estimates into account. RESULTS AND CONCLUSIONS: Between 2010 and 2013 the estimated sensitivity of the overall IPD surveillance increased from 81% to 99%. The sensitivity of individual reporting sources increased from 72% to 87% for the laboratory system and from 31% to 89% for the epidemiological notification system. Crucial for this improvement was the introduction of quarterly report reminders in 2011. Due to positive source dependency, the presented sensitivity estimates are most probably overestimated and reflect the upper limit of reporting completeness. Stratification showed variation in sensitivity of reporting particularly according to region. An effect of the PVC vaccination in the Czech Republic is visible in the incidence of IPD in target age groups (<5 y). This influence was not evident in the total IPD incidence and may interfere with increasing sensitivity of reporting. In 2013, an increase in the IPD incidence was observed. This finding requires further observation and a detailed vaccine impact analysis is needed to assess the current immunization strategy.

An omnibus test for several hazard alternatives in prevention randomized controlled clinical trials.

The logrank test is optimal for testing the equality of survival distributions against a proportional hazards alternative. Under a late effects alternative, it is no longer appropriate, and one may turn to Fleming-Harrington's class of weighted logrank tests instead. In some settings, such as in preventive clinical trials where the statistical analysis has to be designed before the trial begins, it can be difficult to choose a priori between the logrank and Fleming-Harrington tests. A solution to this issue is provided. A decision rule is constructed for the problem of testing the equality of two survival distributions when the expected alternative may be one of the proportional hazards and late effects. A formula for computing the necessary sample size is obtained for this decision rule. A comprehensive simulation study is conducted to assess finite sample properties of the proposed test statistic. The proposed test improves both the logrank test and Fleming-Harrington's test for late effects. Finally, the methodology is illustrated on a data set in the field of prevention of Alzheimer's disease.

Modeling of process parameters for enhanced production of coenzyme Q10 from Rhodotorula glutinis.

Coenzyme Q10 (CoQ10) plays an indispensable role in ATP generation through oxidative phosphorylation and helps in scavenging superoxides generated during electron transfer reactions. It finds extensive applications specifically related to oxidative damage and metabolic dysfunctions. This article reports the use of a statistical approach to optimize the concentration of key variables for the enhanced production of CoQ10 by Rhodotorula glutinis in a lab-scale fermenter. The culture conditions that promote optimum growth and CoQ10 production were optimized and the interaction of significant variables para-hydroxybenzoic acid (PHB, 819.34 mg/L) and soybean oil (7.78% [v/v]) was studied using response surface methodology (RSM). CoQ10 production increased considerably from 10 mg/L (in control) to 39.2 mg/L in batch mode with RSM-optimized precursor concentration. In the fed-batch mode, PHB and soybean oil feeding strategy enhanced CoQ10 production to 78.2 mg/L.

Evidence-informed person-centred health care (part II): are 'cognitive biases plus' underlying the EBM paradigm responsible for undermining the quality of evidence?

INTRODUCTION: Recently, some leaders of the evidence-based medicine (EBM) movement drew attention to the "unintended" negative consequences associated with EBM. The term 'cognitive biases plus' was introduced in part I to encompass cognitive biases, conflicts of interests, fallacies and certain behaviours. HYPOTHESIS: 'Cognitive biases plus' in those closely involved in creating and promoting the EBM paradigm are responsible for their (1) inability to anticipate and then recognize flaws in the tenets of EBM; (2) discounting alternative views; and (3) delaying reform. METHODS: A narrative review style was used, with methods as in part I. APPRAISAL OF LITERATURE: Over the past two decades there has been mounting qualitative and quantitative methodological evidence to suggest that the faith placed in (1) the EBM hierarchy with randomized controlled trials and systematic reviews at the summit; (2) the reliability of biostatistical methods to quantitate data; and (3) the primacy of sources of pre-appraised evidence, is seriously misplaced. Consequently, the evidence that informs person-centred care is compromised. DISCUSSION: Arguments focusing on 'cognitive biases plus' are offered to support our hypothesis. To the best of our knowledge, EBM proponents have not provided an explanation. CONCLUSIONS: Reform is urgently needed to minimize continuing risks to patients. If our hypothesis is correct, then in addition to the suggestions made in part I, deficiencies in the paradigm must be corrected. Meaningful solutions are only possible if the biases of scientific inbreeding and groupthink are minimized by collaboration between EBM leaders and those who have been sounding warning bells.