Sarah H. Landis

High-Throughput Pooling and Real-Time PCR-Based Strategy for Malaria Detection

ABSTRACT Molecular assays can provide critical information for malaria diagnosis, speciation, and drug resistance, but their cost and resource requirements limit their application to clinical malaria studies. This study describes the application of a resource-conserving testing algorithm employing sample pooling for real-time PCR assays for malaria in a cohort of 182 pregnant women in Kinshasa. A total of 1,268 peripheral blood samples were collected during the study. Using a real-time PCR assay that detects all Plasmodium species, microscopy-positive samples were amplified individually; the microscopy-negative samples were amplified after pooling the genomic DNA (gDNA) of four samples prior to testing. Of 176 microscopy-positive samples, 74 were positive by the real-time PCR assay; the 1,092 microscopy-negative samples were initially amplified in 293 pools, and subsequently, 35 samples were real-time PCR positive (3%). With the real-time PCR result as the referent standard, microscopy was 67.9% sensitive (95% confidence interval [CI], 58.3% to 76.5%) and 91.2% specific (95% CI, 89.4% to 92.8%) for malaria. In total, we detected 109 parasitemias by real-time PCR and, by pooling samples, obviated over 50% of reactions and halved the cost of testing. Our study highlights both substantial discordance between malaria diagnostics and the utility and parsimony of employing a sample pooling strategy for molecular diagnostics in clinical and epidemiologic malaria studies.

Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012-2013

Purpose The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000. Materials and methods Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale. Results Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment. Conclusion This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey.

Head and neck cancer in South East England between 1995-1999 and 2000-2004: An estimation of incidence and distribution by site, stage and histological type.

Population-based data on head and neck cancer (HNC) stage and histological type are poorly described for England; these data are essential for clinical management and research. The aim of this study was to describe the distribution and incidence of all HNC and selected anatomical sites by sex, age, stage and histological type using a population-based cancer registry in South East England, and determine if the incidence changed between 1995-1999 and 2000-2004. We identified all HNC cancer cases registered by the Thames Cancer Registry for 1995-1999 and 2000-2004. Frequency distributions and age-standardised incidence rates were calculated by sex, age, stage and histological type and trends in incidence between the two time periods were described using incidence rate ratios and 95% confidence intervals. A total of 8700 HNC cases were reported in 2000-2004, representing an age-standardised incidence rate of 8.59 per 100000, which did not change significantly from 1995-1999. The three commonest HNC sites were intra-oral cavity, larynx and tonsil. Males were two to six times as likely as females to be diagnosed with HNC and there was a trend toward younger age at diagnosis over time. Significant increases in the incidence rate of intra-oral cavity cancer for both sexes and tonsillar cancer among males were observed. Conversely, laryngeal cancer incidence decreased over time. Staging data was only available for about 40% of HNC cases. Seventy six percent of HNC cases were squamous cell carcinomas. Trends in incidence varied between HNC sites, highlighting the importance of presenting data for individual HNC sites. The high proportion of unstaged cancers may result from incomplete recording in medical records; thus, the reporting of staging data should be made a priority.

Impact of maternal malaria and under-nutrition on intrauterine growth restriction: a prospective ultrasound study in Democratic Republic of Congo

Maternal malaria and under-nutrition are established risk factors for small-for-gestational-age (SGA) births; however, whether malaria is associated with intrauterine growth restriction (IUGR) is unknown. We investigated IUGR risk among 177 HIV-negative pregnant women enrolled in a longitudinal ultrasound study conducted in Democratic Republic of Congo from May 2005 to May 2006. Malaria infection, maternal anthropometrics, and ultrasound estimated fetal weight were measured monthly. All positive malaria cases were treated and intermittent presumptive therapy (IPTp) provided. Log-binomial regression models for IUGR were fitted using generalized estimating equations to account for statistical clustering of repeat IUGR measurements. Twenty-nine percent of fetuses experienced an episode of IUGR with the majority occurring in the third trimester. The risk of IUGR associated with malaria was greatest after three or more cumulative infections (RR 3.3, 95% CI 1.3-8.2) and was two- to eight-fold higher among women with evidence of under-nutrition. Receiving antimalarial treatment in the previous month (for IPTp or treatment) was significantly protective against IUGR (RR 0.5, 95% CI 0.3-0.7). The interaction observed between malaria and under-nutrition suggests that antenatal programmes in malaria endemic areas should incorporate nutritional screening and supplementation in addition to IPTp.

Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound study

BackgroundDuring early pregnancy, the placenta develops to meet the metabolic demands of the foetus. The objective of this analysis was to examine the effect of malaria parasitaemia prior to 20 weeks’ gestation on subsequent changes in uterine and umbilical artery blood flow and intrauterine growth restriction.MethodsData were analysed from 548 antenatal visits after 20 weeks’ gestation of 128 women, which included foetal biometric measures and interrogation of uterine and umbilical artery blood flow. Linear mixed effect models estimated the effect of early pregnancy malaria parasitaemia on uterine and umbilical artery resistance indices. Log-binomial models with generalized estimating equations estimated the effect of early pregnancy malaria parasitaemia on the risk of intrauterine growth restriction.ResultsThere were differential effects of early pregnancy malaria parasitaemia on uterine artery resistance by nutritional status, with decreased uterine artery resistance among nourished women with early pregnancy malaria and increased uterine artery resistance among undernourished women with early pregnancy malaria. Among primigravidae, early pregnancy malaria parasitaemia decreased umbilical artery resistance in the late third trimester, likely reflecting adaptive villous angiogenesis. In fully adjusted models, primigravidae with early pregnancy malaria parasitaemia had 3.6 times the risk of subsequent intrauterine growth restriction (95% CI: 2.1, 6.2) compared to the referent group of multigravidae with no early pregnancy malaria parasitaemia.ConclusionsEarly pregnancy malaria parasitaemia affects uterine and umbilical artery blood flow, possibly due to alterations in placentation and angiogenesis, respectively. Among primigravidae, early pregnancy malaria parasitaemia increases the risk of intrauterine growth restriction. The findings support the initiation of malaria parasitaemia prevention and control efforts earlier in pregnancy.

Continuing to Confront COPD International Physician Survey: physician knowledge and application of COPD management guidelines in 12 countries

Aim Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists. Materials and methods Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face. Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios. Results Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001). Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options. The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively. For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively. Conclusion This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines. Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations.

Continuing to Confront COPD International Patient Survey: Economic Impact of COPD in 12 Countries

Background The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries. Using data from this survey we evaluated the economic impact of COPD. Methods This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications. Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale. Combined direct and indirect costs estimated the total societal costs per patient. Results The annual direct costs of COPD ranged from

PREVALENCE AND INCIDENCE OF ACUTE AND CHRONIC COMORBIDITY IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

504 (South Korea) to

Ultrasound‐derived fetal size nomogram for a sub‐Saharan African population: a longitudinal study

9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs. The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%. Total societal costs per patient varied widely from

Continuing to Confront COPD International Surveys: comparison of patient and physician perceptions about COPD risk and management

1,721 (Russia) to