Sharon Sanders

Prevalence of attention-deficit/ Hyperactivity disorder: A systematic review and meta-analysis

BACKGROUND AND OBJECTIVE: Overdiagnosis and underdiagnosis of attention-deficit/hyperactivity disorder (ADHD) are widely debated, fueled by variations in prevalence estimates across countries, time, and broadening diagnostic criteria. We conducted a meta-analysis to: establish a benchmark pooled prevalence for ADHD; examine whether estimates have increased with publication of different editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM); and explore the effect of study features on prevalence. METHODS: Medline, PsycINFO, CINAHL, Embase, and Web of Science were searched for studies with point prevalence estimates of ADHD. We included studies of children that used the diagnostic criteria from DSM-III, DSM-III-R and DSM-IV in any language. Data were extracted on sampling procedure, sample characteristics, assessors, measures, and whether full or partial criteria were met. RESULTS: The 175 eligible studies included 179 ADHD prevalence estimates with an overall pooled estimate of 7.2% (95% confidence interval: 6.7 to 7.8), and no statistically significant difference between DSM editions. In multivariable analyses, prevalence estimates for ADHD were lower when using the revised third edition of the DSM compared with the fourth edition (P = .03) and when studies were conducted in Europe compared with North America (P = .04). Few studies used population sampling with random selection. Most were from single towns or regions, thus limiting generalizability. CONCLUSIONS: Our review provides a benchmark prevalence estimate for ADHD. If population estimates of ADHD diagnoses exceed our estimate, then overdiagnosis may have occurred for some children. If fewer, then underdiagnosis may have occurred.

Development and validation of the Emergency Department Assessment of Chest pain Score and 2 h accelerated diagnostic protocol

Risk scores and accelerated diagnostic protocols can identify chest pain patients with low risk of major adverse cardiac event who could be discharged early from the ED, saving time and costs. We aimed to derive and validate a chest pain score and accelerated diagnostic protocol (ADP) that could safely increase the proportion of patients suitable for early discharge.

Systematic Review of the Diagnostic Accuracy of C-Reactive Protein to Detect Bacterial Infection in Nonhospitalized Infants and Children with Fever

OBJECTIVE To determine the accuracy of C-reactive protein (CRP) for diagnosing serious bacterial and bacterial infections in infants and children presenting with fever. STUDY DESIGN Systematic review of diagnostic accuracy studies. We included studies comparing the diagnostic accuracy of CRP with microbiologic confirmation of (a) serious bacterial and (b) bacterial infection. RESULTS For differentiating between serious bacterial infection and benign or nonbacterial infection (6 studies), the pooled estimate of sensitivity was 0.77 (95% CI, 0.68, 0.83); specificity, 0.79 (95% CI, 0.74, 0.83); positive likelihood ratio, 3.64 (95% CI, 2.99, 4.43); and negative likelihood ratio, 0.29 (95% CI, 0.22, 0.40). In multivariate analysis, CRP is an independent predictor of serious bacterial infection. 3 studies investigating the accuracy of CRP for diagnosing bacterial infection could not be pooled, but all showed a lower sensitivity compared with studies using serious bacterial infection as the reference diagnosis. CONCLUSIONS CRP provides moderate and independent information for both ruling in and ruling out serious bacterial infection in children with fever at first presentation. Poor sensitivity means that CRP cannot be used to exclude all bacterial infection.

Clinical prediction rules in practice: review of clinical guidelines and survey of GPs

BACKGROUND The publication of clinical prediction rules (CPRs) studies has risen significantly. It is unclear if this reflects increasing usage of these tools in clinical practice or how this may vary across clinical areas. AIM To review clinical guidelines in selected areas and survey GPs in order to explore CPR usefulness in the opinion of experts and use at the point of care. DESIGN AND SETTING A review of clinical guidelines and survey of UK GPs. METHOD Clinical guidelines in eight clinical domains with published CPRs were reviewed for recommendations to use CPRs including primary prevention of cardiovascular disease, transient ischaemic attack (TIA) and stroke, diabetes mellitus, fracture risk assessment in osteoporosis, lower limb fractures, breast cancer, depression, and acute infections in childhood. An online survey of 401 UK GPs was also conducted. RESULTS Guideline review: Of 7637 records screened by title and/or abstract, 243 clinical guidelines met inclusion criteria. CPRs were most commonly recommended in guidelines regarding primary prevention of cardiovascular disease (67%) and depression (67%). There was little consensus across various clinical guidelines as to which CPR to use preferentially. SURVEY Of 401 responders to the GP survey, most were aware of and applied named CPRs in the clinical areas of cardiovascular disease and depression. The commonest reasons for using CPRs were to guide management and conform to local policy requirements. CONCLUSION GPs use CPRs to guide management but also to comply with local policy requirements. Future research could focus on which clinical areas clinicians would most benefit from CPRs and promoting the use of robust, externally validated CPRs.

Accuracy of epidemiological inferences based on publicly available information: retrospective comparative analysis of line lists of human cases infected with influenza A(H7N9) in China

BackgroundAppropriate public health responses to infectious disease threats should be based on best-available evidence, which requires timely reliable data for appropriate analysis. During the early stages of epidemics, analysis of ‘line lists’ with detailed information on laboratory-confirmed cases can provide important insights into the epidemiology of a specific disease. The objective of the present study was to investigate the extent to which reliable epidemiologic inferences could be made from publicly-available epidemiologic data of human infection with influenza A(H7N9) virus.MethodsWe collated and compared six different line lists of laboratory-confirmed human cases of influenza A(H7N9) virus infection in the 2013 outbreak in China, including the official line list constructed by the Chinese Center for Disease Control and Prevention plus five other line lists by HealthMap, Virginia Tech, Bloomberg News, the University of Hong Kong and FluTrackers, based on publicly-available information. We characterized clinical severity and transmissibility of the outbreak, using line lists available at specific dates to estimate epidemiologic parameters, to replicate real-time inferences on the hospitalization fatality risk, and the impact of live poultry market closure.ResultsDemographic information was mostly complete (less than 10% missing for all variables) in different line lists, but there were more missing data on dates of hospitalization, discharge and health status (more than 10% missing for each variable). The estimated onset to hospitalization distributions were similar (median ranged from 4.6 to 5.6 days) for all line lists. Hospital fatality risk was consistently around 20% in the early phase of the epidemic for all line lists and approached the final estimate of 35% afterwards for the official line list only. Most of the line lists estimated >90% reduction in incidence rates after live poultry market closures in Shanghai, Nanjing and Hangzhou.ConclusionsWe demonstrated that analysis of publicly-available data on H7N9 permitted reliable assessment of transmissibility and geographical dispersion, while assessment of clinical severity was less straightforward. Our results highlight the potential value in constructing a minimum dataset with standardized format and definition, and regular updates of patient status. Such an approach could be particularly useful for diseases that spread across multiple countries.

A systematic review of studies comparing diagnostic clinical prediction rules with clinical judgment.

Background Diagnostic clinical prediction rules (CPRs) are developed to improve diagnosis or decrease diagnostic testing. Whether, and in what situations diagnostic CPRs improve upon clinical judgment is unclear. Methods and Findings We searched MEDLINE, Embase and CINAHL, with supplementary citation and reference checking for studies comparing CPRs and clinical judgment against a current objective reference standard. We report 1) the proportion of study participants classified as not having disease who hence may avoid further testing and or treatment and 2) the proportion, among those classified as not having disease, who do (missed diagnoses) by both approaches. 31 studies of 13 medical conditions were included, with 46 comparisons between CPRs and clinical judgment. In 2 comparisons (4%), CPRs reduced the proportion of missed diagnoses, but this was offset by classifying a larger proportion of study participants as having disease (more false positives). In 36 comparisons (78%) the proportion of diagnoses missed by CPRs and clinical judgment was similar, and in 9 of these, the CPRs classified a larger proportion of participants as not having disease (fewer false positives). In 8 comparisons (17%) the proportion of diagnoses missed by the CPRs was greater. This was offset by classifying a smaller proportion of participants as having the disease (fewer false positives) in 2 comparisons. There were no comparisons where the CPR missed a smaller proportion of diagnoses than clinical judgment and classified more participants as not having the disease. The design of the included studies allows evaluation of CPRs when their results are applied independently of clinical judgment. The performance of CPRs, when implemented by clinicians as a support to their judgment may be different. Conclusions In the limited studies to date, CPRs are rarely superior to clinical judgment and there is generally a trade-off between the proportion classified as not having disease and the proportion of missed diagnoses. Differences between the two methods of judgment are likely the result of different diagnostic thresholds for positivity. Which is the preferred judgment method for a particular clinical condition depends on the relative benefits and harms of true positive and false positive diagnoses.

Simplification of a scoring system maintained overall accuracy but decreased the proportion classified as low risk

OBJECTIVES Scoring systems are developed to assist clinicians in making a diagnosis. However, their uptake is often limited because they are cumbersome to use, requiring information on many predictors, or complicated calculations. We examined whether, and how, simplifications affected the performance of a validated score for identifying adults with chest pain in an emergency department who have low risk of major adverse cardiac events. STUDY DESIGN AND SETTING We simplified the Emergency Department Assessment of Chest pain Score (EDACS) by three methods: (1) giving equal weight to each predictor included in the score, (2) reducing the number of predictors, and (3) using both methods--giving equal weight to a reduced number of predictors. The diagnostic accuracy of the simplified scores was compared with the original score in the derivation (n = 1,974) and validation (n = 909) data sets. RESULTS There was no difference in the overall accuracy of the simplified versions of the score compared with the original EDACS as measured by the area under the receiver operating characteristic curve (0.74 to 0.75 for simplified versions vs. 0.75 for the original score in the validation cohort). With score cut-offs set to maintain the sensitivity of the combination of score and tests (electrocardiogram and cardiac troponin) at a level acceptable to clinicians (99%), simplification reduced the proportion of patients classified as low risk from 50% with the original score to between 22% and 42%. CONCLUSION Simplification of a clinical score resulted in similar overall accuracy but reduced the proportion classified as low risk and therefore eligible for early discharge compared with the original score. Whether the trade-off is acceptable, will depend on the context in which the score is to be used. Developers of clinical scores should consider simplification as a method to increase uptake, but further studies are needed to determine the best methods of deriving and evaluating simplified scores.

Prescribable mHealth apps identified from an overview of systematic reviews

Mobile health apps aimed towards patients are an emerging field of mHealth. Their potential for improving self-management of chronic conditions is significant. Here, we propose a concept of “prescribable” mHealth apps, defined as apps that are currently available, proven effective, and preferably stand-alone, i.e., that do not require dedicated central servers and continuous monitoring by medical professionals. Our objectives were to conduct an overview of systematic reviews to identify such apps, assess the evidence of their effectiveness, and to determine the gaps and limitations in mHealth app research. We searched four databases from 2008 onwards and the Journal of Medical Internet Research for systematic reviews of randomized controlled trials (RCTs) of stand-alone health apps. We identified 6 systematic reviews including 23 RCTs evaluating 22 available apps that mostly addressed diabetes, mental health and obesity. Most trials were pilots with small sample size and of short duration. Risk of bias of the included reviews and trials was high. Eleven of the 23 trials showed a meaningful effect on health or surrogate outcomes attributable to apps. In conclusion, we identified only a small number of currently available stand-alone apps that have been evaluated in RCTs. The overall low quality of the evidence of effectiveness greatly limits the prescribability of health apps. mHealth apps need to be evaluated by more robust RCTs that report between-group differences before becoming prescribable. Systematic reviews should incorporate sensitivity analysis of trials with high risk of bias to better summarize the evidence, and should adhere to the relevant reporting guideline.

Antibiotics for Children With Acute Otitis Media

In Reply We agree with Mr Dove and Dr Prainsack that an individual’s decision to donate samples and medical information to a biobank is influenced by many factors, including those they describe. That makes it no less true, however, that a decision to donate may also be affected by a large range of moral concerns over future research possibilities, represented only in part by the scenarios presented in our survey. As Dove and Prainstock suggest, that range of possibilities is essentially unlimited and unpredictable, all the more so with the increase of data sharing on an international scale. Individuals who donate to future biobank research during their participation in a clinical trial evaluating new treatments for their medical condition, for example, cannot expect that such research will be confined to that subject. That is why it is common practice in the United States to get a separate consent for the biobank donation that usually gives explicit permission to use it and its associated data in any future research for which it is suitable. Thus, whatever their starting points, most donations of specimens and associated medical information will produce data likely to end up in a research biobank. The willingness to give an open-ended consent is what we were evaluating in our survey. Although some draw a distinction between broad and blanket consent, in either case donors give consent to unknown future uses. The distinction, then, is not pertinent to our finding that willingness to give that consent is affected by the mere possibility of research uses that might be of moral concern to some people.

Legacy Effect of Delayed Blood Pressure-Lowering Pharmacotherapy in Middle-Aged Individuals Stratified by Absolute Cardiovascular Disease Risk: Protocol for a Systematic Review

Background Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease (CVD) should no longer be based on BP level alone, but on absolute cardiovascular risk. While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP, clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain “untreated”. Objective We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals (45-65 years) with mildly elevated BP (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) stratified by absolute risk for primary prevention of CVD, but particularly in the low-risk (<10% five-year absolute risk) group. Methods Randomized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process. First, randomized trials of BP-lowering therapy will be identified by (1) retrieving the references of trials included in published systematic reviews of BP-lowering therapy, (2) retrieving studies published by the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC), and (3) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memorandum on BP management. Posttrial follow-up studies will then be identified by forward citation searching the randomized trials identified in step 1 through Web of Science. The search will include randomized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase. Age is the major determinant of absolute cardiovascular risk, so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile. The primary outcome will be all-cause mortality. Secondary outcomes will include cardiovascular mortality, fatal stroke, fatal myocardial infarction, and death due to heart failure. Results The searches for existing systematic reviews and BPLTTC studies were piloted and modified. The study is expected to be completed before June 2018. Conclusions The findings of this study will contribute to the body of knowledge concerning the beneficial, neutral, or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk. Trial Registration PROSPERO International Prospective Register of Systematic Reviews: CRD42017058414; https://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017058414 (Archived by WebCite® at http://www.webcitation.org/6t6sa8O2Q)