Lucy Anne Parker

Social determinants of smoking in low- and middle-income countries: results from the World Health Survey.

Introduction Tobacco smoking is a leading cause of premature death and disability, and over 80% of the worlds smokers live in low- or middle-income countries. The objective of this study is to assess demographic and socioeconomic determinants of current smoking in low- and middle-income countries. Methods We used data, from the World Health Survey in 48 low-income and middle-income countries, to explore the impact of demographic and socioeconomic factors on the current smoking status of respondents. The data from these surveys provided information on 213,807 respondents aged 18 years or above that were divided into 4 pooled datasets according to their sex and country income group. The overall proportion of current smokers, as well as the proportion by each relevant demographic and socioeconomic determinant, was calculated within each of the pooled datasets, and multivariable logistic regression was used to assess the association between current smoking and these determinants. Results The odds of smoking were not equal in all demographic or socioeconomic groups. Some factors were fairly stable across the four datasets studied: for example, individuals were more likely to smoke if they had little or no education, regardless of if they were male or female, or lived in a low or a middle income country. Nevertheless, other factors, notably age and wealth, showed a differential effect on smoking by sex or country income level. While women in the low-income country group were twice as likely to smoke if they were in the lowest wealth quintile compared with the highest, the association was absent in the middle-income country group. Conclusion Information on how smoking is distributed among low- or middle-income countries will allow policy makers to tailor future policies, and target the most vulnerable populations.

Socioeconomic Inequality in Smoking in Low-Income and Middle-Income Countries: Results from the World Health Survey

Objectives To assess the magnitude and pattern of socioeconomic inequality in current smoking in low and middle income countries. Methods We used data from the World Health Survey [WHS] in 48 low-income and middle-income countries to estimate the crude prevalence of current smoking according to household wealth quintile. A Poisson regression model with a robust variance was used to generate the Relative Index of Inequality [RII] according to wealth within each of the countries studied. Results In males, smoking was disproportionately prevalent in the poor in the majority of countries. In numerous countries the poorest men were over 2.5 times more likely to smoke than the richest men. Socioeconomic inequality in women was more varied showing patterns of both pro-rich and pro-poor inequality. In 20 countries pro-rich relative socioeconomic inequality was statistically significant: the poorest women had a higher prevalence of smoking compared to the richest women. Conversely, in 9 countries women in the richest population groups had a statistically significant greater risk of smoking compared to the poorest groups. Conclusion Both the pattern and magnitude of relative inequality may vary greatly between countries. Prevention measures should address the specific pattern of smoking inequality observed within a population.

Overinterpretation of Clinical Applicability in Molecular Diagnostic Research

BACKGROUND We evaluated whether articles on molecular diagnostic tests interpret appropriately the clinical applicability of their results. METHODS We selected original-research articles published in 2006 that addressed the diagnostic value of a molecular test. We defined overinterpretation of clinical applicability by means of prespecified rules that evaluated study design, conclusions regarding applicability, presence of statements suggesting the need for further clinical evaluation of the test, and diagnostic accuracy. Two reviewers independently evaluated the articles; consensus was reached after discussion and arbitration by a third reviewer. RESULTS Of 108 articles included in the study, 82 (76%) used a design that used healthy controls or alternative-diagnosis controls, only 15 (11%) addressed a clinically relevant population similar to that in which the test might be applied in practice, 104 articles (96%) made definitely favorable or promising statements regarding clinical applicability, and 61 (56%) of the articles apparently overinterpreted the clinical applicability of their findings. Articles published in journals with higher impact factors were more likely to overinterpret their results than those with lower impact factors (adjusted odds ratio, 1.71 per impact factor quartile; 95% CI, 1.09-2.69; P = 0.020). Overinterpretation was more common when authors were based in laboratories than in clinical settings (adjusted odds ratio, 18.7; 95% CI, 1.41-249; P = 0.036). CONCLUSIONS Although expectations are high for new diagnostic tests based on molecular techniques, the majority of published research has involved preclinical phases of research. Overinterpretation of the clinical applicability of findings for new molecular diagnostic tests is common.

Factors Associated with Virological Failure and Suppression after Enhanced Adherence Counselling, in Children, Adolescents and Adults on Antiretroviral Therapy for HIV in Swaziland

Introduction This study explores factors associated with virological detectability, and viral re-suppression after enhanced adherence counselling, in adults and children on antiretroviral therapy (ART) in Swaziland. Methods This descriptive study used laboratory data from 7/5/2012 to 30/9/2013, which were linked with the national ART database to provide information on time on ART and CD4 count; information on enhanced adherence counselling was obtained from file review in health facilities. Multivariable logistic regression was used to explore the relationship between viral load, gender, age, time on ART, CD4 count and receiving (or not receiving) enhanced adherence counselling. Results From 12,063 patients undergoing routine viral load monitoring, 1941 (16%) had detectable viral loads. Children were more likely to have detectable viral loads (AOR 2.6, 95%CI 1.5–4.5), as were adolescents (AOR 3.2, 95%CI 2.2–4.8), patients with last CD4<350 cells/µl (AOR 2.2, 95%CI 1.7–2.9) or WHO Stage 3/4 disease (AOR 1.3, 95%CI 1.1–1.6), and patients on ART for longer (AOR 1.1, 95%CI 1.1–1.2). At retesting, 450 (54% of those tested) showed viral re-suppression. Children were less likely to re-suppress (AOR 0.2, 95%CI 0.1–0.7), as were adolescents (AOR 0.3, 95%CI 0.2–0.8), those with initial viral load> 1000 copies/ml (AOR 0.3, 95%CI 0.1–0.7), and those with last CD4<350 cells/µl (AOR 0.4, 95%CI 0.2–0.7). Receiving (or not receiving) enhanced adherence counselling was not associated with likelihood of re-suppression. Conclusions Children, adolescents and those with advanced disease were most likely to have high viral loads and least likely to achieve viral suppression at retesting; receiving adherence counselling was not associated with higher likelihood of viral suppression. Although the level of viral resistance was not quantified, this study suggests the need for ART treatment support that addresses the adherence problems of younger people; and to define the elements of optimal enhanced adherence support for patients of all ages with detectable viral loads.

Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study

BACKGROUND Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2-4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention. METHODS We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). FINDINGS Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5-100·0) and after adjusting for potential confounders was 87·3% (70·2-100·0). INTERPRETATION One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings. FUNDING Médecins Sans Frontières.

Feasibility and effectiveness of two community-based HIV testing models in rural Swaziland.

To evaluate the feasibility (population reached, costs) and effectiveness (positivity rates, linkage to care) of two strategies of community‐based HIV testing and counselling (HTC) in rural Swaziland.

Methodological Deficits in Diagnostic Research Using '-Omics' Technologies: Evaluation of the QUADOMICS Tool and Quality of Recently Published Studies

Background QUADOMICS is an adaptation of QUADAS (a quality assessment tool for use in systematic reviews of diagnostic accuracy studies), which takes into account the particular challenges presented by ‘-omics’ based technologies. Our primary objective was to evaluate the applicability and consistency of QUADOMICS. Subsequently we evaluated and describe the methodological quality of a sample of recently published studies using the tool. Methodology/Principal Findings 45‘-omics’- based diagnostic studies were identified by systematic search of Pubmed using suitable MeSH terms (“Genomics”, “Sensitivity and specificity”, “Diagnosis”). Three investigators independently assessed the quality of the articles using QUADOMICS and met to compare observations and generate a consensus. Consistency and applicability was assessed by comparing each reviewers original rating with the consensus. Methodological quality was described using the consensus rating. Agreement was above 80% for all three reviewers. Four items presented difficulties with application, mostly due to the lack of a clearly defined gold standard. Methodological quality of our sample was poor; studies met roughly half of the applied criteria (mean ± sd, 54.7±18.4%). Few studies were carried out in a population that mirrored the clinical situation in which the test would be used in practice, (6, 13.3%); none described patient recruitment sufficiently; and less than half described clinical and physiological factors that might influence the biomarker profile (20, 44.4%). Conclusions The QUADOMICS tool can consistently be applied to diagnostic ‘-omics’ studies presently published in biomedical journals. A substantial proportion of reports in this research field fail to address design issues that are fundamental to make inferences relevant for patient care.

Impact and programmatic implications of routine viral load monitoring in Swaziland.

Objective:To assess the programmatic quality (coverage of testing, counseling, and retesting), cost, and outcomes (viral suppression, treatment decisions) of routine viral load (VL) monitoring in Swaziland. Design:Retrospective cohort study of patients undergoing routine VL monitoring in Swaziland (October 1, 2012 to March 31, 2013). Results:Of 5563 patients eligible for routine VL testing monitoring in the period of study, an estimated 4767 patients (86%) underwent testing that year. Of 288 patients with detectable VL, 210 (73%) underwent enhanced adherence counseling and 202 (70%) had a follow-up VL within 6 months. Testing coverage was slightly lower in children, but coverage of retesting was similar between and age groups and sexes. Of those with a follow-up test, 126 (62%) showed viral suppression. The remaining 78 patients had World Health Organization–defined virologic failure; 41 (53%) were referred by the doctor for more adherence counseling, and 13 (15%) were changed to second-line therapy, equating to an estimated rate of 1.2 switches per 100 patient-years. Twenty-four patients (32%) were transferred out, lost to follow-up, or not reviewed by doctor. The “fully loaded” cost of VL monitoring was

Sources of error and its control in studies on the diagnostic accuracy of "-omics" technologies.

35 per patient-year. Conclusions:Achieving good quality VL monitoring is feasible and affordable in resource-limited settings, although close supervision is needed to ensure good coverage of testing and counseling. The low rate of switch to second-line therapy in patients with World Health Organization–defined virologic failure seems to reflect clinician suspicion of ongoing adherence problems. In our study, the main impact of routine VL monitoring was reinforcing adherence rather than increasing use of second-line therapy.

Adapting to the global shortage of cholera vaccines: targeted single dose cholera vaccine in response to an outbreak in South Sudan

Analyses of errors in diagnostic studies have led to improvements in the methodological quality of traditional laboratory research. However, since features of genomics and proteomics research (“‐omics”) differ from those of traditional research, sources of error are also likely to be distinct. We examine the main sources of error that are particularly relevant to “‐omics”‐based diagnostic techniques through the analysis of primary research papers which address these potential errors, their solutions, and the resulting spurious effect on diagnostic accuracy prediction. The main sources of error described in “‐omics”‐based research are mainly associated with chance: overfitting and inadequate sample size; variation: preanalytical variation (specimen collection and management), analytical variation (test procedures and reproducibility) and biological variation. We conclude that “‐omics”‐based research is prone to several errors. We have characterized them and shown the range of available solutions. This is a key step in the application of genomic discoveries to clinical and public health practice.