The Effectiveness of a Community-Based Mentoring Program for Children Aged 5-11 Years: Results from a Randomized Controlled Trial.

The study, a two-arm, randomized controlled, parallel group, superiority trial, aimed to evaluate the implementation and effectiveness of a 12-month one-to-one volunteer mentoring program designed to improve behavioral and emotional outcomes in children aged 5 to 11 years who have teacher- and parent/carer-reported behavioral difficulties. Participants were 246 children (123 intervention, 123 control; mean age 8.4 years; 87% boys) in five sites in London, UK, scoring in the "abnormal" range on the teacher-rated Strengths and Difficulties Questionnaire (SDQ) Total Difficulties measure and in the "borderline" or abnormal range on the parent-rated SDQ Total Difficulties measure. Randomization on a 1:1 ratio took place using a computer-generated sequence and stratifying by site. Data collectors and statisticians were blind to participant allocation status. Outcome measures focused on parent- and teacher-rated child behavior and emotions, and child-rated self-perception and hope. Intention-to-treat analysis on all 246 randomized participants (using imputed data where necessary) showed that at post-intervention (16 months after randomization), there were no statistically significant effects on the primary outcome-parent-rated SDQ Total Difficulties (adjusted standardized mean difference = - 0.12; 95% CI: -0.38 to 0.13; p = 0.33)-or any secondary outcomes. Results from complier average causal effect (CACE) analysis using the primary outcome indicated the intervention was not effective for children who received the recommended duration of mentoring. Exploratory analyses found no sub-group effects on the primary outcome. The article concludes that the mentoring program had no effect on children's behavior or emotional well-being, and that program content needs revising to satisfactorily address key risk and protective factors.

An overview of malarial Anopheles mosquito survival estimates in relation to methodology.

BACKGROUND: The transmission of malaria is known to be sensitive to the survival (longevity, mortality) of its mosquito vector, yet there have been few reviews of estimates of this important population parameter in the malaria-carrying genus Anopheles. METHODS: We carried out a systematic search for and meta-analysis of survival estimates, framed around the methods of estimation, under the major groupings of ?vertical' (based on stable age or stage frequencies), ?horizontal' (based on recaptures of marked and released cohorts), and ?parasitological' (proportion of infectious mosquitoes). Because of the intricacies of the estimation process we provide an outline of these methods. RESULTS: By meta-analysis we quantify the average of the distribution of daily survival [Formula: see text] for vertical (0.83, 95% CI: 0.80-0.86), horizontal (0.73, 95% CI: 0.66-0.79) and parasitological (0.92, 95% CI: 0.86-0.95) methods. CONCLUSIONS: The meta-analysis demonstrates the anticipated result that horizontal estimates are lowest because they estimate apparent survival (survival and non-emigration) rather than true survival. On the other hand, vertical methods make strong assumptions about the stability or stationarity of the underlying populations. Further potential sources of methodological bias are mentioned. The substantial differences in estimates between methods indicates that methodological biases need to be considered when making use of available survival estimates.

Patient-initiated appointment systems for adults with chronic conditions in secondary care.

BACKGROUND: Missed hospital outpatient appointments is a commonly reported problem in healthcare services around the world; for example, they cost the National Health Service (NHS) in the UK millions of pounds every year and can cause operation and scheduling difficulties worldwide. In 2002, the World Health Organization (WHO) published a report highlighting the need for a model of care that more readily meets the needs of people with chronic conditions. Patient-initiated appointment systems may be able to meet this need at the same time as improving the efficiency of hospital appointments. OBJECTIVES: To assess the effects of patient-initiated appointment systems compared with consultant-led appointment systems for people with chronic or recurrent conditions managed in secondary care. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and six other databases. We contacted authors of identified studies and conducted backwards and forwards citation searching. We searched for current/ongoing research in two trial registers. Searches were run on 13 March 2019. SELECTION CRITERIA: We included randomised trials, published and unpublished in any language that compared the use of patient-initiated appointment systems to consultant-led appointment systems for adults with chronic or recurrent conditions managed in secondary care if they reported one or more of the following outcomes: physical measures of health status or disease activity (including harms), quality of life, service utilisation or cost, adverse effects, patient or clinician satisfaction, or failures of the 'system'. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references at title/abstract stage and full-text stage using prespecified inclusion criteria. We resolved disagreements though discussion. Two review authors independently completed data extraction for all included studies. We discussed and resolved discrepancies with a third review author. Where needed, we contacted authors of included papers to provide more information. Two review authors independently assessed the risk of bias using the Cochrane Effective Practice and Organisation of Care 'Risk of bias' tool, resolving any discrepancies with a third review author. Two review authors independently assessed the certainty of the evidence using GRADE. MAIN RESULTS: The 17 included randomised trials (3854 participants; mean age 41 to 76 years; follow-up 12 to 72 months) covered six broad health conditions: cancer, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, psoriasis and inflammatory bowel disease. The certainty of the evidence using GRADE ratings was mainly low to very low. The results suggest that patient-initiated clinics may make little or no difference to anxiety (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.68 to 1.12; 5 studies, 1019 participants; low-certainty evidence) or depression (OR 0.79 95% CI 0.51 to 1.23; 6 studies, 1835 participants; low-certainty evidence) compared to the consultant-led appointment system. The results also suggest that patient-initiated clinics may make little or no difference to quality of life (standardised mean difference (SMD) 0.12, 95% CI 0.00 to 0.25; 7 studies, 1486 participants; low-certainty evidence) compared to the consultant-led appointment system. Results for service utilisation (contacts) suggest there may be little or no difference in service utilisation in terms of contacts between the patient-initiated and consultant-led appointment groups; however, the effect is not certain as the rate ratio ranged from 0.68 to 3.83 across the studies (median rate ratio 1.11, interquartile (IQR) 0.93 to 1.37; 15 studies, 3348 participants; low-certainty evidence). It is uncertain if service utilisation (costs) are reduced in the patient-initiated compared to the consultant-led appointment groups (8 studies, 2235 participants; very low-certainty evidence). The results suggest that adverse events such as relapses in some conditions (inflammatory bowel disease and cancer) may have little or no reduction in the patient-initiated appointment group in comparison with the consultant-led appointment group (MD -0.20, 95% CI -0.54 to 0.14; 3 studies, 888 participants; low-certainty evidence). The results are unclear about any differences the intervention may make to patient satisfaction (SMD 0.05, 95% CI -0.41 to 0.52; 2 studies, 375 participants) because the certainty of the evidence is low, as each study used different questions to collect their data at different time points and across different health conditions. Some areas of risk of bias across all the included studies was consistently high (i.e. for blinding of participants and personnel and blinding of outcome assessment, other areas were largely of low risk of bias or were affected by poor reporting making the assessment unclear). AUTHORS' CONCLUSIONS: Patient-initiated appointment systems may have little or no effect on patient anxiety, depression and quality of life compared to consultant-led appointment systems. Other aspects of disease status and experience also appear to show little or no difference between patient-initiated and consultant-led appointment systems. Patient-initiated appointment systems may have little or no effect on service utilisation in terms of service contact and there is uncertainty about costs compared to consultant-led appointment systems. Patient-initiated appointment systems may have little or no effect on adverse events such as relapse or patient satisfaction compared to consultant-led appointment systems.

The Effectiveness of the KiVa Bullying Prevention Program in Wales, UK: Results from a Pragmatic Cluster Randomized Controlled Trial.

The study evaluated the implementation fidelity and effectiveness of KiVa, an evidence-based program that aims to prevent and address bullying in schools, with a particular emphasis on changing the role of bystanders. The study was a two-arm waitlist control cluster randomized controlled trial in which 22 primary schools (clusters) (N = 3214 students aged 7-11) were allocated using a 1:1 ratio to intervention (KiVa; 11 clusters, n = 1588 students) and a waitlist control (usual school provision; 11 clusters, n = 1892 children)). The trial statistician (but not schools or researchers) remained blind to allocation status. The outcomes were as follows: student-reported victimization (primary outcome) and bullying perpetration; teacher-reported child behavior and emotional well-being; and school absenteeism (administrative records). Implementation fidelity was measured using teacher-completed online records (for class lessons) and independent researcher observations (for school-wide elements). Outcome analyses involved 11 intervention schools (n = 1578 children) and 10 control schools (n = 1636 children). There was no statistically significant effect on the primary outcome of child-reported victimization (adjusted intervention/control OR 0.76; 95% CI 0.55 to 1.06; p = 0.11) or on the secondary outcomes. The impact on victimization was not moderated by child gender, age, or victimization status at baseline. Lesson adherence was good but exposure (lesson length) was lower than the recommended amount, and there was considerable variability in the implementation of whole school elements. The trial found insufficient evidence to conclude that KiVa had an effect on the primary outcome. A larger trial of KiVa in the UK is warranted, however, with attention to issues regarding implementation fidelity. Trial registration: Current Controlled Trials ISRCTN23999021 Date 10-6-13.

The use of anterior subcutaneous internal fixation (INFIX) for treatment of pelvic ring injuries in major trauma patients, complications and outcomes.

PURPOSE: Pelvic anterior internal fixators (INFIX) are a relatively new alternative in the treatment of unstable pelvic fractures. The authors wanted to review the use of complications and outcomes of this method of pelvic fixation at our institution. METHOD: Patients over the age of 18 who had an INFIX used in treatment of their pelvic ring injury were identified. Patient demographics, fracture type, injury severity score, morbidity, complications and time until removal were recorded. All available patients were followed up following the removal of the INFIX and completed an Iowa Pelvic Score (IPS) at this time. RESULTS AND DISCUSSION: 24 patients (19 male) with a mean age of 38.5 (range 18-71) met the inclusion criteria with an average injury severity score of 29.8 (10-66). The most common complication following insertion was a lateral femoral cutaneous nerve (LFCN) injury, which occurred in 11 patients (bilaterally in two), 6 patients (25%) had ongoing numbness 6 months post removal. Two patients had an infection, one of which prompted the removal of the INFIX. One INFIX was removed for implant failure. All other removals were planned electively. Heterotopic ossification was noted to have occurred in five cases. The mean IPS following removal of the INFIX was 79.2 (52-100). INFIX is a safe and successful treatment for unstable pelvic ring injuries. Overall, patients tolerate the INFIX well with good outcome scores. The main concern being the high rate of LFCN injuries, although many resolved after removal of the INFIX.

Bacteriological profile of community-acquired musculoskeletal infections: a study from Queensland.

BACKGROUND: The purpose of this study was to determine bacteriology of community-acquired musculoskeletal infections requiring hospitalization and to compare this with published national and international data. This will help treating physicians select the appropriate antibiotic. METHODS: All patients who underwent surgical procedures for community-acquired musculoskeletal infections over a period of 22 months were included in the study. Hospital acquired infections, post-operative infections and infections involving prosthetic joints were excluded. Patient characteristics, treatment details, cultured organisms and their antibiotic sensitivity were recorded. RESULTS: Forty-five patients with 46 cases met the inclusion criteria. Ten patients were from paediatric age group. Soft tissue infections were the most common diagnosis and accounted for 20 cases. The remainder were septic arthritis (n = 17) and osteomyelitis (n = 9). Thirteen patients (28.3%) had negative cultures from the operative samples. Staphylococcus aureus was the most common isolated organism overall accounting for 23 cases (69.7%). Methicillin-resistant S. aureus (MRSA) sensitive to vancomycin was cultured in four adult cases (12.1%), of which three were hand infections (50%). For the entire cohort, 67.7% and 61.3% isolates that were tested were sensitive to cefazolin and flucloxacillin, respectively. CONCLUSION: The bacteriological profile in this study is consistent with European and Australian data. While the overall MRSA infection rate was low, it was much higher among hand infections and is comparable to reports from the USA. Flucloxacillin and cefazolin should be considered as the first line of antibiotic therapy for all cases. Vancomycin should be considered when MRSA is suspected.

The effectiveness of Chance UK's mentoring programme in improving behavioural and emotional outcomes in primary school children with behavioural difficulties: study protocol for a randomised controlled trial.

BACKGROUND: There is a need to build the evidence base of early interventions to promote children's health and development in the UK. Chance UK is a voluntary sector organisation based in London that delivers a 12-month mentoring programme for primary school children identified by teachers and parents as having behavioural and emotional difficulties. The aim of the study is to determine the effectiveness of the programme in terms of children's behaviour and emotional well-being; this is the primary outcome of the trial. METHODS/DESIGN: A randomised controlled trial will be conducted in which participants are randomly allocated on a dynamic basis to one of two possible arms: the intervention arm (n = 123) will be offered the mentoring programme, and the control arm (n = 123) will be offered services as usual. Outcome data will be collected at three points: pre-intervention (baseline), mid-way through the mentoring year (c.9 months after randomisation) and post- mentoring programme (c.16 months after randomisation). DISCUSSION: This study will further enhance the evidence for early intervention mentoring programmes for child behaviour and emotional well-being in the UK. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47154925 . Retrospectively registered 9 September 2014.

The effectiveness of the Inspiring Futures parenting programme in improving behavioural and emotional outcomes in primary school children with behavioural or emotional difficulties: study protocol for a randomised controlled trial.

BACKGROUND: There is a need to build the evidence base of early interventions promoting children's health and development in the UK. Malachi Specialist Family Support Services ('Malachi') is a voluntary sector organisation based in the UK that delivers a therapeutic parenting group programme called Inspiring Futures to parents of children identified as having behavioural and emotional difficulties. The programme comprises two parts, delivered sequentially: (1) a group-based programme for all parents for 10-12 weeks, and (2) one-to-one sessions with selected parents from the group-based element for up to 12 weeks. METHODS/DESIGN: A randomised controlled trial will be conducted to evaluate Malachi's Inspiring Futures parenting programme. Participants will be allocated to one of two possible arms, with follow-up measures at 16 weeks (post-parent group programme) and at 32 weeks (post-one-to-one sessions with selected parents). The sample size is 248 participants with a randomisation allocation ratio of 1:1. The intervention arm will be offered the Inspiring Futures programme. The control group will receive services as usual. The aim is to determine the effectiveness of the Inspiring Futures programme on the primary outcome of behavioural and emotional difficulties of primary school children identified as having behavioural or emotional difficulties. DISCUSSION: This study will further enhance the evidence for early intervention parenting programmes for child behavioural and emotional problems in the UK. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32083735 . Retrospectively registered 28 October 2014.

Maternal thyroid hormone insufficiency during pregnancy and risk of neurodevelopmental disorders in offspring: A systematic review and meta-analysis.

BACKGROUND: In the last 2 decades, several studies have examined the association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children and shown conflicting results. AIM: This systematic review aimed to assess the evidence for an association between maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental disorders in children. We also sought to assess whether levothyroxine treatment for maternal thyroid hormone insufficiency improves child neurodevelopment outcomes. METHODS: We performed systematic literature searches in MEDLINE, EMBASE, PSYCinfo, CINAHL, AMED, BNI, Cochrane, Scopus, Web of Science, GreyLit, Grey Source and Open Grey (latest search: March 2017). We also conducted targeted web searching and performed forwards and backwards citation chasing. Meta-analyses of eligible studies were carried out using the random-effects model. RESULTS: We identified 39 eligible articles (37 observational studies and 2 randomized controlled trials [RCT]). Meta-analysis showed that maternal subclinical hypothyroidism and hypothyroxinaemia are associated with indicators of intellectual disability in offspring (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.20 to 3.83, P = .01, and OR 1.63, 95% CI 1.03 to 2.56, P = .04, respectively). Maternal subclinical hypothyroidism and hypothyroxinaemia were not associated with attention deficit hyperactivity disorder, and their effect on the risk of autism in offspring was unclear. Meta-analysis of RCTs showed no evidence that levothyroxine treatment for maternal hypothyroxinaemia or subclinical hypothyroidism reduces the incidence of low intelligence quotient in offspring. LIMITATIONS: Although studies were generally of good quality, there was evidence of heterogeneity between the included observational studies (I2 72%-79%). CONCLUSION: Maternal hypothyroxinaemia and subclinical hypothyroidism may be associated with intellectual disability in offspring. Currently, there is no evidence that levothyroxine treatment, when initiated 8- to 20-week gestation (mostly between 12 and 17 weeks), for mild maternal thyroid hormone insufficiency during pregnancy reduces intellectual disability in offspring.

Variation in ambulance call rates for care homes in Torbay, UK.

Emergency ambulance calls represent one of the routes of emergency hospital admissions from care homes. We aimed to describe the pattern of ambulance call rates from care homes and identify factors predicting those homes calling for an ambulance most frequently. We obtained data from South Western Ambulance Service NHS Foundation Trust on 3138 ambulance calls relating to people aged 65 and over from care homes in the Torbay region between 1 April 2012 and 31 July 2013. We supplemented this with data from the Care Quality Commission (CQC) website on home characteristics and outcomes of CQC inspections. We used descriptive statistics to identify variation in ambulance call rates for residential and nursing homes and fitted negative binomial regression models to determine if call rates were predicted by home type (nursing versus residential), the five standards in the CQC reports, dementia care status or travel time to hospital. One hundred and forty-six homes (119 residential and 27 nursing) were included in the analysis. The number of calls made ranged from 1 to 99. The median number (IQR; range) of calls per resident per year was 0.51 (0.21-0.89; 0.03-2.45). Nursing homes had a lower call rate than residential homes [adjusted rate ratio (ARR) 0.29; 95% CI: 0.22-0.40; P < 0.001]; care homes failing the quality and suitability of management standard had a lower call rate compared to those who passed (ARR 0.67; 95% CI: 0.50-0.90; P = 0.006); and homes specialising in dementia had a higher call rate compared to those not specialising (ARR 1.56; 95% CI: 1.23-1.96; P < 0.001). These findings require replication in other regions to establish their generalisability and further investigation is required to determine the extent to which call rate variability reflects the different needs of resident populations or differences in care home policies and practice.

Effectiveness and micro-costing of the KiVa school-based bullying prevention programme in Wales: study protocol for a pragmatic definitive parallel group cluster randomised controlled trial.

BACKGROUND: Bullying refers to verbal, physical or psychological aggression repeated over time that is intended to cause harm or distress to the victims who are unable to defend themselves. It is a key public health priority owing to its widespread prevalence in schools and harmful short- and long-term effects on victims' well-being. There is a need to strengthen the evidence base by testing innovative approaches to preventing bullying. KiVa is a school-based bullying prevention programme with universal and indicated elements and an emphasis on changing bystander behaviour. It achieved promising results in a large trial in Finland, and now requires testing in other countries. This paper describes the protocol for a cluster randomised controlled trial (RCT) of KiVa in Wales. METHODS/DESIGN: The study uses a two-arm waitlist control pragmatic definitive parallel group cluster RCT design with an embedded process evaluation and calculation of unit cost. Participating schools will be randomised a using a 1:1 ratio to KiVa plus usual provision (intervention group) or usual provision only (control group). The trial has one primary outcome, child self-reported victimisation from bullying, dichotomised as 'victimised' (bullied at least twice a month in the last couple of months) versus 'not victimised'. Secondary outcomes are: bullying perpetration; aspects of child social and emotional well-being (including emotional problems, conduct, peer relations, prosocial behaviour); and school attendance. Follow-up is at 12 months post-baseline. Implementation fidelity is measured through teacher-completed lesson records and independent school-wide observation. A micro-costing analysis will determine the costs of implementing KiVa, including recurrent and non-recurrent unit costs. Factors related to the scalability of the programme will be examined in interviews with head teachers and focus groups with key stakeholders in the implementation of school-based bullying interventions. DISCUSSION: The results from this trial will provide evidence on whether the KiVa programme is transportable from Finland to Wales in terms of effectiveness and implementation. It will provide information about the costs of delivery and generate insights into factors related to the scalability of the programme. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23999021 Date 10-6-13.

Psychological interventions to improve psychological well-being in people with dementia or mild cognitive impairment: systematic review and meta-analysis protocol.

INTRODUCTION: Dementia and mild cognitive impairment are associated with an increased risk of depression, anxiety, psychological distress and poor mental health-related quality of life. However, there is a lack of research examining the evidence base for psychological interventions targeting general psychological well-being within this population. Furthermore, there is little research relating to the design of randomised controlled trials examining psychological interventions for dementia and mild cognitive impairment, such as effective recruitment techniques, trial eligibility and appropriate comparators. METHODS AND ANALYSIS: Systematic review of electronic databases (CINAHL; EMBASE; PsychInfo; MEDLINE; ASSIA and CENTRAL), supplemented by expert contact, reference and citation checking, and grey literature searches. Published and unpublished studies will be eligible for inclusion with no limitations placed on year of publication. Primary outcomes of interest will be standardised measurements of depression, anxiety, psychological distress or mental health-related quality of life. Eligibility and randomisation proportions will be calculated as secondary outcomes. If data permits, meta-analytical techniques will examine: (1) overall effectiveness of psychological interventions for people with dementia or mild cognitive impairment in relation to outcomes of depression, anxiety, psychological distress or mental health-related quality of life; (2) clinical and methodological moderators associated with effectiveness; (3) proportions eligible, recruited and randomised. ETHICS AND DISSEMINATION: Ethical approval is not required for the present systematic review. Results will inform the design of a feasibility study examining a new psychological intervention for people with dementia and depression, with dissemination through publication in peer-reviewed journals and presentations at relevant conferences. TRIAL REGISTRATION NUMBER: CRD42015025177.

Sleep positioning systems for children with cerebral palsy.

BACKGROUND: Sleep positioning systems can be prescribed for children with cerebral palsy to help reduce or prevent hip migration, provide comfort to ease pain and/or improve sleep. As sleep disturbance is common in children with developmental disabilities, with impact on their carers' sleep, and as sleep positioning systems can be expensive, guidance is needed to support decisions as to their use. OBJECTIVES: To determine whether commercially-available sleep positioning systems, compared with usual care, reduce or prevent hip migration in children with cerebral palsy. Any negative effect of sleep positioning systems on hip migration will be considered within this objective.Secondary objectives were to determine the effect of sleep positioning systems on: (1) number or frequency of hip problems; (2) sleep patterns and quality; (3) quality of life of the child and family; (4) pain; and (5) physical functioning. We also sought to identify any adverse effects from using sleep positioning systems. SEARCH METHODS: In December 2014, we searched CENTRAL, Ovid MEDLINE, Embase, and 13 other databases. We also searched two trials registers. We applied no restrictions on date of publication, language, publication status or study design. We checked references and contacted manufacturers and authors for potentially relevant literature, and searched the internet using Google. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) evaluating whole body sleep positioning systems for children and adolescents (up to 18 years of age) with cerebral palsy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened reports retrieved from the search against pre-determined inclusion criteria and assessed the quality of eligible studies.Members of the public (parent carers of children with neurodisability) contributed to this review by suggesting the topic, refining the research objectives, interpreting the findings, and reviewing the plain language summary. MAIN RESULTS: We did not identify any randomised controlled trials that evaluated the effectiveness of sleep positioning systems on hip migration.We did find two randomised cross-over trials that met the inclusion criteria in respect of secondary objectives relating to sleep quality and pain. Neither study reported any important difference between sleeping in sleep positioning systems and not for sleep patterns or sleep quality (two studies, 21 children, very low quality evidence) and pain (one study, 11 children, very low quality evidence). These were small studies with established users of sleep positioning systems and were judged to have high risk of bias.We found no eligible trials that explored the other secondary objectives (number or frequency of hip problems, quality of life of the child and family, physical functioning, and adverse effects). AUTHORS' CONCLUSIONS: We found no randomised trials that evaluated the effectiveness of sleep positioning systems to reduce or prevent hip migration in children with cerebral palsy. Nor did we find any randomised trials that evaluated the effect of sleep positioning systems on the number or frequency of hip problems, quality of life of the child and family or on physical functioning.Limited data from two randomised trials, which evaluated the effectiveness of sleep positioning systems on sleep quality and pain for children with cerebral palsy, showed no significant differences in these aspects of health when children were using and not using a sleep positioning system.In order to inform clinical decision-making and the prescription of sleep positioning systems, more rigorous research is needed to determine effectiveness, cost-effectiveness, and the likelihood of adverse effects.

Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

BACKGROUND: Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings. OBJECTIVE: To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. METHODS: Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. RESULTS: Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects'): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. LIMITATIONS: Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. CONCLUSION: A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical association, but also public health relevance, novelty, and biological plausibility. Although this strategy needs to be further evaluated using other healthcare data sources, the list of 'prime suspects' makes a good starting point for further clinical, laboratory, and epidemiologic investigation.

Using electronic health care records for drug safety signal detection: a comparative evaluation of statistical methods.

BACKGROUND: Drug safety monitoring relies primarily on spontaneous reporting, but electronic health care record databases offer a possible alternative for the detection of adverse drug reactions (ADRs). OBJECTIVES: To evaluate the relative performance of different statistical methods for detecting drug-adverse event associations in electronic health care record data representing potential ADRs. RESEARCH DESIGN: Data from 7 databases across 3 countries in Europe comprising over 20 million subjects were used to compute the relative risk estimates for drug-event pairs using 10 different methods, including those developed for spontaneous reporting systems, cohort methods such as the longitudinal gamma poisson shrinker, and case-based methods such as case-control. The newly developed method "longitudinal evaluation of observational profiles of adverse events related to drugs" (LEOPARD) was used to remove associations likely caused by protopathic bias. Data from the different databases were combined by pooling of data, and by meta-analysis for random effects. A reference standard of known ADRs and negative controls was created to evaluate the performance of the method. MEASURES: The area under the curve of the receiver operator characteristic curve was calculated for each method, both with and without LEOPARD filtering. RESULTS: The highest area under the curve (0.83) was achieved by the combination of either longitudinal gamma poisson shrinker or case-control with LEOPARD filtering, but the performance between methods differed little. LEOPARD increased the overall performance, but flagged several known ADRs as caused by protopathic bias. CONCLUSIONS: Combinations of methods demonstrate good performance in distinguishing known ADRs from negative controls, and we assume that these could also be used to detect new drug safety signals.

Cognition and belief in paranormal phenomena: gestalt/feature-intensive processing theory and tendencies toward ADHD, depression, and dissociation.

Belief in paranormal phenomena and cryptids--unknown animals such as Bigfoot--may predispose individuals to interpret real-world objects and events in the same way that eyewitness identification can be biased by unrelated information (P. James and N. Thorpe, 1999). Psychological tendencies toward attention deficit hyperactivity disorder (ADHD), dissociation, and depression, even at subclinical levels, may be associated systematically with particular paranormal or cryptozoological beliefs. The authors evaluated these psychological tendencies using the Conners Adult ADHD Rating Scales (C. K. Conners, D. Erhardt, and E. Sparrow, 1999), the Dissociative Experiences Scale (L. Coleman & J. Clark, 1999), and the Beck Depression Inventory-II (A. T. Beck, 1996). They performed regression analyses against beliefs in ghosts, unidentified flying objects (UFOs), extrasensory perception (ESP), astrology, and cryptids. ADHD, dissociation, and depression were associated with enhanced tendencies toward paranormal and cryptozoological beliefs, although participants who believed in each of the phenomena differed from one another in predictable and psychologically distinguishable ways. Cognitively biasing influences of preexisting psychological tendencies may predispose individuals to specific perceptual and cognitive errors during confrontation of real-world phenomena.