A survey of barriers and facilitators to ultrasound use in low- and middle-income countries.

Point-of-care ultrasound has the potential to help inform assessment, diagnosis, and management of illness in low- and middle-income countries (LMIC). To better understand current ultrasound use, barriers and facilitators to use, and perceptions and practices in LMIC, we conducted an anonymous online global survey targeting healthcare providers training and using ultrasound in LMIC. A total of 241 respondents representing 62 countries participated and most were physicians working in publicly-funded urban tertiary hospitals in LMIC. Most had received ultrasound training (78%), reported expertise (65%) and confidence (90%) in ultrasound use, and had access to ultrasound (88%), utilizing ultrasound most commonly for procedures and for evaluations of lungs, heart, and trauma. Access to an ultrasound machine was reported as both the top barrier (17%) and top facilitator (53%); other common barriers included access to education and training, cost, and competition for use and other common facilitators included access to a probe, gel, and electricity, and acceptance by healthcare providers, administrators, and patients. Most (80%) noted ultrasound access was important and 96% agreed that ultrasound improves quality of care and patient outcomes. Improving access to low-cost ultrasound equipment is critical to increasing ultrasound use among those who are trained.

Effectiveness of the 10-valent pneumococcal conjugate vaccine on pediatric pneumonia confirmed by ultrasound: a matched case-control study.

BACKGROUND: Bangladesh introduced the 10-valent pneumococcal conjugate vaccine (PCV10) for children aged < 1 year in March 2015. Previous vaccine effectiveness (VE) studies for pneumonia have used invasive pneumococcal disease or chest X-rays. None have used ultrasound. We sought to determine the VE of PCV10 against sonographically-confirmed pneumonia in three subdistrict health complexes in Bangladesh. METHODS: We conducted a matched case-control study between July 2015 and September 2017 in three subdistricts of Sylhet, Bangladesh. Cases were vaccine-eligible children aged 3-35 months with sonographically-confirmed pneumonia, who were matched with two types of controls by age, sex, week of diagnosis, subdistrict health complex (clinic controls) or distance from subdistrict health complex (community controls) and had an illness unlikely due to Streptococcus pneumoniae (clinic controls) or were healthy (community controls). VE was measured using multivariable conditional logistic regression. RESULTS: We evaluated 8926 children (average age 13.3 months, 58% boys) with clinical pneumonia by ultrasound; 2470 had pneumonia with consolidations ≥ 1 cm; 1893 pneumonia cases were matched with 4238 clinic controls; and 1832 were matched with 3636 community controls. VE increased with the threshold used for consolidation size on ultrasound: the adjusted VE of ≥ 2 doses vs. non-recipients of PCV10 against pneumonia increased from 15.8% (95% CI 1.6-28.0%) for consolidations ≥ 1 cm to 29.6% (12.8-43.2%) for consolidations ≥ 1.5 cm using clinic controls and from 2.7% (- 14.2-17.2%) to 23.5% (4.4-38.8%) using community controls, respectively. CONCLUSIONS: PCV10 was effective at reducing sonographically-confirmed pneumonia in children aged 3-35 months of age when compared to unvaccinated children. VE increased with the threshold used for consolidation size on ultrasound in clinic and community controls alike. This study provides evidence that lung ultrasound is a useful alternative to chest X-ray for case-control studies evaluating the effectiveness of vaccines against pneumonia.

Effectiveness of the 10-valent pneumococcal conjugate vaccine against radiographic pneumonia among children in rural Bangladesh: A case-control study.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh. METHODS: We conducted a matched case-control study over two years from 2015 to 2017 using clinic and community controls in three subdistricts of Sylhet, Bangladesh. Cases were vaccine eligible 3-35 month olds at Upazila Health Complex outpatient clinics with World Health Organization-defined radiographic primary endpoint pneumonia (radiographic pneumonia). Clinic controls were matched to cases within a one week time window by age, sex, and clinic and had an illness unlikely to be Streptococcus pneumoniae; community controls were healthy and similarly matched within a one week time window by age and sex, and distance from the clinic. We estimated adjusted vaccine effectiveness (aVE) using conditional logistic regression. RESULTS: We matched 1262 cases with 2707 clinic and 2461 community controls. Overall, aVE using clinic controls was 21.4% (95% confidence interval, -0.2%, 38.4%) for ≥2 PCV10 doses and among 3-11 month olds was 47.3% (10.5%, 69.0%) for three doses. aVE increased with higher numbers of doses in clinic control sets (p = 0.007). In contrast, aVE using community controls was 7.6% (95% confidence interval, -22.2%, 30.0%) for ≥2 doses. We found vaccine introduction in the study area faster and less variable than expected with 75% coverage on average, which reduced power. Information bias may also have affected community controls. CONCLUSIONS: Clinic control analyses show PCV10 prevented radiographic pneumonia in Bangladesh, especially among younger children receiving three doses. While both analyses were underpowered, community control enrollment - compared to clinic controls - was more difficult in a complex, pluralistic healthcare system. Future studies in comparable settings may consider alternative study designs.

Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group.

Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.

Training and standardization of general practitioners in the use of lung ultrasound for the diagnosis of pediatric pneumonia.

BACKGROUND: Pneumonia is a leading cause of death in children of low-resource settings. Barriers to care include an early and accurate diagnosis. Lung ultrasound is a novel tool for the identification of pediatric pneumonia; however, there is currently no standardized approach to train in image acquisition and interpretation of findings in epidemiological studies. We developed a training program for physicians with limited ultrasound experience on how to use ultrasound for the diagnosis of pediatric pneumonia and how to standardize image interpretation using a panel of readers. METHODS: Twenty-five physicians participating in the training program conducted lung ultrasounds in all children with suspected pneumonia, aged 3 to 35 months, presenting to three subdistrict hospitals in Sylhet, Bangladesh, between June 2015 and September 2017. RESULTS: A total of 9051 pediatric lung ultrasound assessments were conducted through 27 months of data collection. Study physicians underwent training and all were successfully standardized, achieving 91% agreement and maintained a sensitivity and specificity of 88% and 92%, respectively, when their diagnosis was compared with experts. Overall kappa between two readers was high (0.86, 95% confidence interval [CI], 0.84-0.87), and remained high when a third expert reader was included (0.80, 95% CI, 0.79-0.81). Agreement and kappa statistics were similarly high when stratified by age, sex, presence of danger signs, or hypoxemia. CONCLUSIONS: Lung ultrasound is a novel tool for the diagnosis of pediatric pneumonia with evidence supporting its validity and feasibility of implementation. Here we introduced a training program that resulted in a high level of inter-sonographer agreement.

Chest radiograph reading panel performance in a Bangladesh pneumococcal vaccine effectiveness study.

Introduction: To evaluate WHO chest radiograph interpretation processes during a pneumococcal vaccine effectiveness study of children aged 3-35 months with suspected pneumonia in Sylhet, Bangladesh. Methods: Eight physicians masked to all data were standardised to WHO methodology and interpreted chest radiographs between 2015 and 2017. Each radiograph was randomly assigned to two primary readers. If the primary readers were discordant for image interpretability or the presence or absence of primary endpoint pneumonia (PEP), then another randomly selected, masked reader adjudicated the image (arbitrator). If the arbitrator disagreed with both primary readers, or concluded no PEP, then a masked expert reader finalised the interpretation. The expert reader also conducted blinded quality control (QC) for 20% of randomly selected images. We evaluated agreement between primary readers and between the expert QC reading and the final panel interpretation using per cent agreement, unadjusted Cohen's kappa, and a prevalence and bias-adjusted kappa. Results: Among 9723 images, the panel classified 21.3% as PEP, 77.6% no PEP and 1.1% uninterpretable. Two primary readers agreed on interpretability for 98% of images (kappa, 0.25; prevalence and bias-adjusted kappa, 0.97). Among interpretable radiographs, primary readers agreed on the presence or absence of PEP in 79% of images (kappa, 0.35; adjusted kappa, 0.57). Expert QC readings agreed with final panel conclusions on the presence or absence of PEP for 92.9% of 1652 interpretable images (kappa, 0.75; adjusted kappa, 0.85). Conclusion: Primary reader performance and QC results suggest the panel effectively applied the WHO chest radiograph criteria for pneumonia.

Building a Prediction Model for Radiographically Confirmed Pneumonia in Peruvian Children: From Symptoms to Imaging.

BACKGROUND: Community-acquired pneumonia remains the leading cause of death in children worldwide, and current diagnostic guidelines in resource-poor settings are neither sensitive nor specific. We sought to determine the ability to correctly diagnose radiographically confirmed clinical pneumonia when diagnostics tools were added to clinical signs and symptoms in a cohort of children with acute respiratory illnesses in Peru. METHODS: Children < 5 years of age with an acute respiratory illness presenting to a tertiary hospital in Lima, Peru, were enrolled. The ability to predict radiographically confirmed clinical pneumonia was assessed using logistic regression under four additive scenarios: clinical signs and symptoms only, addition of lung auscultation, addition of oxyhemoglobin saturation (Spo2), and addition of lung ultrasound. RESULTS: Of 832 children (mean age, 21.3 months; 59% boys), 453 (54.6%) had clinical pneumonia and 221 (26.6%) were radiographically confirmed. Children with radiographically confirmed clinical pneumonia had lower average Spo2 than those without (95.9% vs 96.6%, respectively; P < .01). The ability to correctly identify radiographically confirmed clinical pneumonia using clinical signs and symptoms was limited (area under the curve [AUC] = 0.62; 95% CI, 0.58-0.67) with a sensitivity of 66% (95% CI, 59%-73%) and specificity of 53% (95% CI, 49%-57%). The addition of lung auscultation improved classification (AUC = 0.73; 95% CI, 0.69-0.77) with a sensitivity of 75% (95% CI, 69%-81%) and specificity of 53% (95% CI, 49%-57%) for the presence of crackles. In contrast, the addition of Spo2 did not improve classification (AUC = 0.73; 95% CI, 0.69-0.77) with a sensitivity of 40% (95% CI, 33%-47%) and specificity of 72% (95% CI, 68%-75%) for an Spo2 ≤ 92%. Adding consolidation on lung ultrasound was associated with the largest improvement in classification (AUC = 0.85; 95% CI, 0.82-0.89) with a sensitivity of 55% (95% CI, 48%-63%) and specificity of 95% (95% CI, 93%-97%). CONCLUSIONS: The addition of lung ultrasound and auscultation to clinical signs and symptoms improved the ability to correctly classify radiographically confirmed clinical pneumonia. Implementation of auscultation- and ultrasound-based diagnostic tools can be considered to improve diagnostic yield of pneumonia in resource-poor settings.

Pneumococcal Conjugate Vaccine impact assessment in Bangladesh.

The study examines the impact of the introduction of 10-valent Pneumococcal Conjugate Vaccine (PCV10) into Bangladesh's national vaccine program. PCV10 is administered to children under 1 year-old; the scheduled ages of administration are at 6, 10, and 18 weeks. The study is conducted in ~770,000 population containing ~90,000 <5 children in Sylhet, Bangladesh and has five objectives: 1) To collect data on community-based pre-PCV incidence rates of invasive pneumococcal diseases (IPD) in 0-59 month-old children in Sylhet, Bangladesh; 2) To evaluate the effectiveness of PCV10 introduction on Vaccine Type (VT) IPD in 3-59 month-old children using an incident case-control study design. Secondary aims include measuring the effects of PCV10 introduction on all IPD in 3-59 month-old children using case-control study design, and quantifying the emergence of Non Vaccine Type IPD; 3) To evaluate the effectiveness of PCV10 introduction on chest radiograph-confirmed pneumonia in children 3-35 months old using incident case-control study design. We will estimate the incidence trend of clinical and radiologically-confirmed pneumonia in 3-35 month-old children in the study area before and after introduction of PCV10; 4) To determine the feasibility and utility of lung ultrasound for the diagnosis of pediatric pneumonia in a large sample of children in a resource-limited setting. We will also evaluate the effectiveness of PCV10 introduction on ultrasound-confirmed pneumonia in 3-35 month-old children using an incident case-control design and to examine the incidence trend of ultrasound-confirmed pneumonia in 3-35 month-old children in the study area before and after PCV10 introduction; and 5) To determine the direct and indirect effects of vaccination status on nasopharyngeal colonization on VT pneumococci among children with pneumonia .  This paper presents the methodology. The study will allow us to conduct a comprehensive and robust assessment of the impact of national introduction of PCV10 on pneumococcal disease in Bangladesh.

Lung ultrasound as a diagnostic tool for radiographically-confirmed pneumonia in low resource settings.

BACKGROUND: Pneumonia is a leading cause of morbidity and mortality in children worldwide; however, its diagnosis can be challenging, especially in settings where skilled clinicians or standard imaging are unavailable. We sought to determine the diagnostic accuracy of lung ultrasound when compared to radiographically-confirmed clinical pediatric pneumonia. METHODS: Between January 2012 and September 2013, we consecutively enrolled children aged 2-59 months with primary respiratory complaints at the outpatient clinics, emergency department, and inpatient wards of the Instituto Nacional de Salud del Niño in Lima, Peru. All participants underwent clinical evaluation by a pediatrician and lung ultrasonography by one of three general practitioners. We also consecutively enrolled children without respiratory symptoms. Children with respiratory symptoms had a chest radiograph. We obtained ancillary laboratory testing in a subset. RESULTS: Final clinical diagnoses included 453 children with pneumonia, 133 with asthma, 103 with bronchiolitis, and 143 with upper respiratory infections. In total, CXR confirmed the diagnosis in 191 (42%) of 453 children with clinical pneumonia. A consolidation on lung ultrasound, which is our primary endpoint for pneumonia, had a sensitivity of 88.5%, specificity of 100%, and an area under-the-curve of 0.94 (95% CI 0.92-0.97) when compared to radiographically-confirmed clinical pneumonia. When any abnormality on lung ultrasound was compared to radiographically-confirmed clinical pneumonia the sensitivity increased to 92.2% and the specificity decreased to 95.2%, with an area under-the-curve of 0.94 (95% CI 0.91-0.96). CONCLUSIONS: Lung ultrasound had high diagnostic accuracy for the diagnosis of radiographically-confirmed pneumonia. Added benefits of lung ultrasound include rapid testing and high inter-rater agreement. Lung ultrasound may serve as an alternative tool for the diagnosis of pediatric pneumonia.

Mortality and reintervention following elective abdominal aortic aneurysm repair.

BACKGROUND: The objective of this study is to provide an up-to-date meta-analysis on the short- and long-term mortality rates of elective repair of abdominal aortic aneurysms (AAAs) via the open and endovascular approaches. METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled trials, conference proceeding from major vascular meetings were searched for randomized trials comparing open vs elective endovascular aneurysm repair (EVAR) of AAAs. A random-effects model was used for analysis. Risk ratio (RR) and 95% confidence intervals (CIs) of open vs EVAR were calculated for short- and long-term mortality and reintervention rates. RESULTS: The analysis encompassed four randomized controlled trials with a total of 2783 patients. The open repair group resulted in significantly increased 30-day postoperative all-cause mortality compared with EVAR repair group (3.2% vs 1.2%; RR, 2.81; 95% CI, 1.60-4.94); however, there is no statistical difference in the long-term all-cause mortality between both groups (RR, 0.97; 95% CI, 0.86-1.10). Interestingly, fewer patients underwent reintervention procedures in the open repair group compared with those who had EVAR repair (9.3% vs 18.9%; RR, 0.49; 95% CI, 0.40-0.60), but this finding is doubtful due to the large heterogeneity. Lastly, no statistical difference in long-term mortality rates attributable to cardiovascular disease (CVD), aneurysm related, or stroke were found between the two types of repair. CONCLUSIONS: Results of this meta-analysis demonstrate that the 30-day all-cause mortality rate is higher with open than with EVAR repair; however, there is no statistical difference in the long-term all-cause and cause-specific mortality between both groups. The reintervention rate attributable to procedural complication was higher in the EVAR group. Because of the equivalency of long-term outcomes and the short-term benefits of EVAR, an endovascular-first approach to AAAs can be supported by the meta-analysis.

Available energy from soft drinks: more than the sum of its parts.

OBJECTIVE: To evaluate the relationship between energy available from sugar-sweetened beverages (SSB) and total energy availability. DESIGN: Ecological study using food availability data from 1976 to 2007 from the database of the Canadian Socio-Economic Information Management System. The average available total daily energy per capita (kJ (kcal)/d per capita) and percentage of energy from SSB (%E/d per capita) were calculated. A regression analysis was performed with average available total daily energy per capita (kJ (kcal)/d per capita) as the outcome and percentage of energy from SSB as the independent variable (%E/d per capita). SETTING: Canada 1976-2007. SUBJECTS: None. RESULTS: Between 1976 and 2007, total available energy increased on average by 669 kJ (160 kcal)/d per capita, and energy from SSB by 155 kJ (37 kcal)/d per capita. Total available energy increased by 434 kJ (104 kcal)/d per capita for a one unit increase in average percentage of energy from SSB. CONCLUSIONS: Total available energy increased as the contribution of energy available from SSB increased. This increase was larger than that explained by energy availability from SSB alone. Reducing energy from soft drinks may contribute to larger reductions in total energy available for consumption.