A Comparison of Machine Learning Algorithms for the Surveillance of Autism Spectrum Disorder

The Centers for Disease Control and Prevention (CDC) coordinates a labor-intensive process to measure the prevalence of autism spectrum disorder (ASD) among children in the United States. Random forests methods have shown promise in speeding up this process, but they lag behind human classification accuracy by about 5%. We explore whether more recently available document classification algorithms can close this gap. We applied 8 supervised learning algorithms to predict whether children meet the case definition for ASD based solely on the words in their evaluations. We compared the algorithms' performance across 10 random train-test splits of the data, using classification accuracy, F1 score, and number of positive calls to evaluate their potential use for surveillance. Across the 10 train-test cycles, the random forest and support vector machine with Naive Bayes features (NB-SVM) each achieved slightly more than 87% mean accuracy. The NB-SVM produced significantly more false negatives than false positives (P = 0.027), but the random forest did not, making its prevalence estimates very close to the true prevalence in the data. The best-performing neural network performed similarly to the random forest on both measures. The random forest performed as well as more recently available models like the NB-SVM and the neural network, and it also produced good prevalence estimates. NB-SVM may not be a good candidate for use in a fully-automated surveillance workflow due to increased false negatives. More sophisticated algorithms, like hierarchical convolutional neural networks, may not be feasible to train due to characteristics of the data. Current algorithms might perform better if the data are abstracted and processed differently and if they take into account information about the children in addition to their evaluations

Vaginal flora morphotypic profiles and assessment of bacterial vaginosis in women at risk for HIV infection.

Specific morphotypic profiles of normal and abnormal vaginal flora, including bacterial vaginosis (BV), were characterized. A prospective study of 350 women yielded concurrent Gram-stain data and clinical assessment (n = 3455 visits). Microbiological profiles were constructed by Gram stain. Eight profile definitions were based on dichotomizing the levels of Lactobacillus, Gardnerella, and curved, Gram-negative bacillus (Mobiluncus) morphotypes. Of these, two were rare, and the other six demonstrated a graded association with the clinical components of BV. The proposed profiles from the Gram stain reflect the morphotypic categories describing vaginal flora that may enable clearer elucidation of gynecologic and obstetric outcomes in various populations

Using Formative Research to Develop a Context-Specific Approach to Informed Consent for Clinical Trials

Participant understanding is of particular concern when obtaining informed consent. Recommendations for improving understanding include disclosing information using culturally appropriate and innovative approaches. To increase the effectiveness of the consent process for a clinical trial in Malawi on interventions to prevent mother-to-child transmission of HIV during breastfeeding, formative research was conducted to explore the community’s understanding of medical research as well as how to explain research through local terms and meanings. Contextual analogies and other approaches were identified to explain consent information. Guided by theory, strategies for developing culturally appropriate interventions, and recommendations from the literature, we demonstrate how the formative data were used to develop culturally appropriate counseling cards specifically for the trial in Malawi. With appropriate contextual modifications, the steps outlined here could be applied in other clinical trials conducted elsewhere, as well as in other types of research

Geographic Differences in Time to Culture Conversion in Liquid Media: Tuberculosis Trials Consortium Study 28. Culture Conversion Is Delayed in Africa

Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding.In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites.African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found.Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved.ClinicalTrials.gov NCT00144417

Improving Participant Understanding of Informed Consent in an HIV-Prevention Clinical Trial: A Comparison of Methods

Empirical research on informed consent has shown that study participants often do not fully understand consent information. This study assessed participant understanding of three mock consent approaches describing an HIV-prevention clinical trial in Lilongwe, Malawi prior to trial implementation. Pregnant women (n = 297) were systematically selected from antenatal-care waiting lines and sequentially allocated to receive an enhanced standard consent form (group 1), a context-specific consent form (group 2), or context-specific counseling cards (group 3). Understanding of research concepts and study procedures was assessed immediately postintervention and at 1-week follow-up. At postintervention, participants in groups 2 and 3 understood more about research concepts and study procedures compared with group 1. Group 3 participants also understood more about study procedures compared with group 2. At follow-up, participants in groups 2 and 3 continued to understand more about research concepts and study procedures. Context-specific approaches improved understanding of consent information in this study

Mycobacterium tuberculosis bloodstream infection prevalence, diagnosis, and mortality risk in seriously ill adults with HIV: a systematic review and meta-analysis of individual patient data.

BACKGROUND: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis bloodstream infection (BSI) is incompletely understood. We hypothesised that M tuberculosis BSI prevalence has been underestimated, that it independently predicts death, and that sputum Xpert MTB/RIF has suboptimal diagnostic yield for M tuberculosis BSI. METHODS: We did a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood culture in a prospectively defined patient population of people with HIV aged 13 years or older. Studies were identified through searching PubMed and Scopus up to Nov 10, 2018, without language or date restrictions and through manual review of reference lists. Risk of bias in the included studies was assessed with an adapted QUADAS-2 framework. IPD were requested for all identified studies and subject to harmonised inclusion criteria: age 13 years or older, HIV positivity, available CD4 cell count, a valid mycobacterial blood culture result (excluding patients with missing data from lost or contaminated blood cultures), and meeting WHO definitions for suspected tuberculosis (presence of screening symptom). Predicted probabilities of M tuberculosis BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum testing with Xpert (or culture if Xpert was unavailable) and of urine lipoarabinomannan (LAM) testing for M tuberculosis BSI were obtained by two-level random-effect meta-analysis. Estimates of mortality associated with M tuberculosis BSI were obtained by mixed-effect Cox proportional-hazard modelling and of effect of treatment delay on mortality by propensity-score analysis. This study is registered with PROSPERO, number 42016050022. FINDINGS: We identified 23 datasets for inclusion (20 published and three unpublished at time of search) and obtained IPD from 20, representing 96·2% of eligible IPD. Risk of bias for the included studies was assessed to be generally low except for on the patient selection domain, which was moderate in most studies. 5751 patients met harmonised IPD-level inclusion criteria. Technical factors such as number of blood cultures done, timing of blood cultures relative to blood sampling, and patient factors such as inpatient setting and CD4 cell count, explained significant heterogeneity between primary studies. The predicted probability of M tuberculosis BSI in hospital inpatients with HIV-associated tuberculosis, WHO danger signs, and a CD4 count of 76 cells per μL (the median for the cohort) was 45% (95% CI 38-52). The diagnostic yield of sputum in patients with M tuberculosis BSI was 77% (95% CI 63-87), increasing to 89% (80-94) when combined with urine LAM testing. Presence of M tuberculosis BSI compared with its absence in patients with HIV-associated tuberculosis increased risk of death before 30 days (adjusted hazard ratio 2·48, 95% CI 2·05-3·08) but not after 30 days (1·25, 0·84-2·49). In a propensity-score matched cohort of participants with HIV-associated tuberculosis (n=630), mortality increased in patients with M tuberculosis BSI who had a delay in anti-tuberculosis treatment of longer than 4 days compared with those who had no delay (odds ratio 3·15, 95% CI 1·16-8·84). INTERPRETATION: In critically ill adults with HIV-tuberculosis, M tuberculosis BSI is a frequent manifestation of tuberculosis and predicts mortality within 30 days. Improved diagnostic yield in patients with M tuberculosis BSI could be achieved through combined use of sputum Xpert and urine LAM. Anti-tuberculosis treatment delay might increase the risk of mortality in these patients. FUNDING: This study was supported by Wellcome fellowships 109105Z/15/A and 105165/Z/14/A

Development of a Standardized Screening Rule for Tuberculosis in People Living with HIV in Resource-Constrained Settings: Individual Participant Data Meta-analysis of Observational Studies

Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease

Mind the gap:TB trends in the USA and the UK, 2000-2011

BACKGROUND: TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries. METHODS: We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends. FINDINGS: A total of 259 609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100 000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100 000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (p<0.01). Among the foreign-born, significant differences in trend were also associated with time since UK or US entry (p<0.01). INTERPRETATION: To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research