Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 56 Records) |
Query Trace: Rees J[original query] |
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Surveillance system integration: reporting the results of a global multicountry survey
Carter ED , Stewart DE , Rees EE , Bezuidenhoudt JE , Ng V , Lynes S , Desenclos JC , Pyone T , Lee ACK . Public Health 2024 231 31-38 OBJECTIVES: Currently, there is no comprehensive picture of the global surveillance landscape. This survey examines the current state of surveillance systems, levels of integration, barriers and opportunities for the integration of surveillance systems at the country level, and the role of national public health institutes (NPHIs). STUDY DESIGN: This was a cross-sectional survey of NPHIs. METHODS: A web-based survey questionnaire was disseminated to 110 NPHIs in 95 countries between July and August 2022. Data were descriptively analysed, stratified by World Health Organization region, World Bank Income Group, and self-reported Integrated Disease Surveillance (IDS) maturity status. RESULTS: Sixty-five NPHIs responded. Systems exist to monitor notifiable diseases and vaccination coverage, but less so for private, pharmaceutical, and food safety sectors. While Ministries of Health usually lead surveillance, in many countries, NPHIs are also involved. Most countries report having partially developed IDS. Surveillance data are frequently inaccessible to the lead public health agency and seldomly integrated into a national public health surveillance system. Common challenges to establishing IDS include information technology system issues, financial constraints, data sharing and ownership limitations, workforce capacity gaps, and data availability. CONCLUSIONS: Public health surveillance systems across the globe, although built on similar principles, are at different levels of maturity but face similar developmental challenges. Leadership, ownership and governance, supporting legal mandates and regulations, as well as adherence to mandates, and enforcement of regulations are critical components of effective surveillance. In many countries, NPHIs play a significant role in integrated disease surveillance. |
Experience on postmortem minimally invasive tissue sampling to ascertain the cause of death determination in South African children: A case for implementing as standard of care
Du Toit J , Storath K , Dunn I , Makekeng P , Moosa M , Mothibi K , Umuneza N , Rees CA , Blau D , Lala S , Adam Y , Velaphi S , Hale M , Swart P , Wadula J , Mothibi L , Wise A , Baba V , Jaglal P , Mahtab S , Madhi S , Dangor Z . S Afr Med J 2024 114 (2) e1538 Determining the death burden for prioritising public health interventions necessitates detailed data on the causal pathways to death. Postmortem minimally invasive tissue sampling (MITS), incorporating histology, molecular and microbial culture diagnostics, enhances cause-of-death attribution, particularly for infectious deaths. MITS proves a valid alternative to full diagnostic autopsies, especially in low- and middle-income countries. In Soweto, South Africa (SA), the Child Health and Mortality Prevention Surveillance (CHAMPS) programme has delineated over 1 000 child and stillbirth deaths since 2017. This SA CHAMPS site supports advocating for the use of postmortem MITS as routine practice, for more granular insights into under-5 mortality causes. This knowledge is crucial for SA's pursuit of Sustainable Development Goal 3.2, targeting reduced neonatal and under-5 mortality rates. This commentary explores the public health advantages and ethicolegal considerations surrounding implementing MITS as standard of care for stillbirths, neonatal and paediatric deaths in SA. Furthermore, based on the data from CHAMPS, we present three pragmatic algorithmic approaches to the wide array of testing options for cost-effectiveness and scalability of postmortem MITS in South African state facilities. |
Identifying delays in healthcare seeking and provision: The Three Delays-in-Healthcare and mortality among infants and children aged 1-59 months
Garcia Gomez E , Igunza KA , Madewell ZJ , Akelo V , Onyango D , El Arifeen S , Gurley ES , Hossain MZ , Chowdhury MAI , Islam KM , Assefa N , Scott JAG , Madrid L , Tilahun Y , Orlien S , Kotloff KL , Tapia MD , Keita AM , Mehta A , Magaço A , Torres-Fernandez D , Nhacolo A , Bassat Q , Mandomando I , Ogbuanu I , Cain CJ , Luke R , Kamara SIB , Legesse H , Madhi S , Dangor Z , Mahtab S , Wise A , Adam Y , Whitney CG , Mutevedzi PC , Blau DM , Breiman RF , Tippett Barr BA , Rees CA . PLOS Glob Public Health 2024 4 (2) e0002494 Delays in illness recognition, healthcare seeking, and in the provision of appropriate clinical care are common in resource-limited settings. Our objective was to determine the frequency of delays in the "Three Delays-in-Healthcare", and factors associated with delays, among deceased infants and children in seven countries with high childhood mortality. We conducted a retrospective, descriptive study using data from verbal autopsies and medical records for infants and children aged 1-59 months who died between December 2016 and February 2022 in six sites in sub-Saharan Africa and one in South Asia (Bangladesh) and were enrolled in Child Health and Mortality Prevention Surveillance (CHAMPS). Delays in 1) illness recognition in the home/decision to seek care, 2) transportation to healthcare facilities, and 3) the receipt of clinical care in healthcare facilities were categorized according to the "Three Delays-in-Healthcare". Comparisons in factors associated with delays were made using Chi-square testing. Information was available for 1,326 deaths among infants and under 5 children. The majority had at least one identified delay (n = 854, 64%). Waiting >72 hours after illness recognition to seek health care (n = 422, 32%) was the most common delay. Challenges in obtaining transportation occurred infrequently when seeking care (n = 51, 4%). In healthcare facilities, prescribed medications were sometimes unavailable (n = 102, 8%). Deceased children aged 12-59 months experienced more delay than infants aged 1-11 months (68% vs. 61%, P = 0.018). Delays in seeking clinical care were common among deceased infants and children. Additional study to assess the frequency of delays in seeking clinical care and its provision among children who survive is warranted. |
Delayed plasmodium falciparum malaria in pregnant patient with sickle cell trait 11 years after exposure, Oregon, USA
Drummond W , Rees K , Ladd-Wilson S , Mace KE , Blackall D , Sutton M . Emerg Infect Dis 2024 30 (1) 151-154 Delayed Plasmodium falciparum malaria in immigrants from disease-endemic countries is rare. Such cases pose a challenge for public health because mosquitoborne transmission must be rigorously investigated. We report a case of delayed P. falciparum malaria in a pregnant woman with sickle cell trait 11 years after immigration to the United States. |
Provider adherence to clinical care recommendations for infants and children who died in seven low- and middle-income countries in the Child Health and Mortality Prevention Surveillance (CHAMPS) network
Rees CA , Igunza KA , Madewell ZJ , Akelo V , Onyango D , El Arifeen S , Gurley ES , Hossain MZ , Rahman A , Alam M , Scott JAG , Assefa N , Madrid L , Belachew A , Leulseged H , Kotloff KL , Sow SO , Tapia MD , Keita AM , Sidibe D , Sitoe A , Varo R , Ajanovic S , Bassat Q , Mandomando I , Tippett Barr BA , Ogbuanu I , Cain CJ , Bassey IA , Luke R , Gassama K , Madhi S , Dangor Z , Mahtab S , Velaphi S , du Toit J , Mutevedzi PC , Blau DM , Breiman RF , Whitney CG . EClinicalMedicine 2023 63 102198 BACKGROUND: Most childhood deaths globally are considered preventable through high-quality clinical care, which includes adherence to clinical care recommendations. Our objective was to describe adherence to World Health Organization recommendations for the management of leading causes of death among children. METHODS: We conducted a retrospective, descriptive study examining clinical data for children aged 1-59 months who were hospitalized and died in a Child Health and Mortality Prevention Surveillance (CHAMPS) catchment, December 2016-June 2021. Catchment areas included: Baliakandi and Faridpur, Bangladesh; Kersa, Haramaya, and Harar, Ethiopia; Kisumu and Siaya, Kenya; Bamako, Mali; Manhiça and Quelimane, Mozambique; Makeni, Sierra Leone; Soweto, South Africa. We reviewed medical records of those who died from lower respiratory tract infections, sepsis, malnutrition, malaria, and diarrheal diseases to determine the proportion who received recommended treatments and compared adherence by hospitalization duration. FINDINGS: CHAMPS enrolled 460 hospitalized children who died from the leading causes (median age 12 months, 53.0% male). Median hospital admission was 31 h. There were 51.0% (n = 127/249) of children who died from lower respiratory tract infections received supplemental oxygen. Administration of intravenous fluids for sepsis (15.9%, n = 36/226) and supplemental feeds for malnutrition (14.0%, n = 18/129) were uncommon. There were 51.4% (n = 55/107) of those who died from malaria received antimalarials. Of the 80 children who died from diarrheal diseases, 76.2% received intravenous fluids. Those admitted for ≥24 h more commonly received antibiotics for lower respiratory tract infections and sepsis, supplemental feeds for malnutrition, and intravenous fluids for sepsis than those admitted <24 h. INTERPRETATION: Provision of recommended clinical care for leading causes of death among young children was suboptimal. Further studies are needed to understand the reasons for deficits in clinical care recommendation adherence. FUNDING: Bill & Melinda Gates Foundation. |
Stability of lipids in plasma and serum: Effects of temperature-related storage conditions on the human lipidome
Reis GB , Rees JC , Ivanova AA , Kuklenyik Z , Drew NM , Pirkle JL , Barr JR . J Mass Spectrom Adv Clin Lab 2021 22 34-42 Large epidemiological studies often require sample transportation and storage, presenting unique considerations when applying advanced lipidomics techniques. The goal of this study was to acquire lipidomics data on plasma and serum samples stored at potential preanalytical conditions (e.g., thawing, extracting, evaporating), systematically monitoring lipid species for a period of one month. Split aliquots of 10 plasma samples and 10 serum samples from healthy individuals were kept in three temperature-related environments: refrigerator, laboratory benchtop, or heated incubator. Samples were analyzed at six different time points over 28 days using a Bligh & Dyer lipid extraction protocol followed by direct infusion into a lipidomics platform using differential mobility with tandem mass spectrometry. The observed concentration changes over time were evaluated relative to method and inter-individual biological variability. In addition, to evaluate the effect of lipase enzyme levels on concentration changes during storage, we compared corresponding fasting and post-prandial plasma samples collected from 5 individuals. Based on our data, a series of low abundance free fatty acid (FFA), diacylglycerol (DAG), and cholesteryl ester (CE) species were identified as potential analytical markers for degradation. These FFA and DAG species are typically produced by endogenous lipases from numerous triacylglycerols (TAGs), and certain high abundance phosphatidylcholines (PCs). The low concentration CEs, which appeared to increase several fold, were likely mass-isobars from oxidation of other high concentration CEs. Although the concentration changes of the high abundant TAG, PC, and CE precursors remained within method variability, the concentration trends of FFA, DAG, and oxidized CE products should be systematically monitored over time to inform analysts about possible pre-analytical biases due to degradation in the study sample sets. |
In-hospital mortality risk stratification in children under 5 years old with pneumonia with or without pulse oximetry: A secondary analysis of the Pneumonia REsearch Partnership To Assess WHO REcommendations (PREPARE) dataset
Hooli S , King C , McCollum ED , Colbourn T , Lufesi N , Mwansambo C , Gregory CJ , Thamthitiwat S , Cutland C , Madhi SA , Nunes MC , Gessner BD , Hazir T , Mathew JL , Addo-Yobo E , Chisaka N , Hassan M , Hibberd PL , Jeena P , Lozano JM , MacLeod WB , Patel A , Thea DM , Nguyen NTV , Zaman SM , Ruvinsky RO , Lucero M , Kartasasmita CB , Turner C , Asghar R , Banajeh S , Iqbal I , Maulen-Radovan I , Mino-Leon G , Saha SK , Santosham M , Singhi S , Awasthi S , Bavdekar A , Chou M , Nymadawa P , Pape JW , Paranhos-Baccala G , Picot VS , Rakoto-Andrianarivelo M , Rouzier V , Russomando G , Sylla M , Vanhems P , Wang J , Basnet S , Strand TA , Neuman MI , Arroyo LM , Echavarria M , Bhatnagar S , Wadhwa N , Lodha R , Aneja S , Gentile A , Chadha M , Hirve S , O'Grady KF , Clara AW , Rees CA , Campbell H , Nair H , Falconer J , Williams LJ , Horne M , Qazi SA , Nisar YB . Int J Infect Dis 2023 129 240-250 OBJECTIVES: We determined pulse oximetry benefit in pediatric pneumonia mortality-risk stratification and chest indrawing pneumonia in-hospital mortality risk factors. METHODS: We report characteristics and in-hospital pneumonia-related mortality of children 2-59-months-old included in the Pneumonia Research Partnership to Assess WHO Recommendations dataset. We developed multivariable logistic regression models of chest indrawing pneumonia to identify mortality risk factors. RESULTS: Among 285,839 children, 164,244 (57·5%) from hospital-based studies were included. Pneumonia case fatality risk (CFR) without pulse oximetry measurement was higher than with measurement (5·8%, 95% CI 5·6-5·9% vs 2·1%, 95% CI 1·9-2·4%). One in five children with chest indrawing pneumonia was hypoxemic (19·7%, 95% CI 19·0-20·4%) and the hypoxemic CFR was 10·3% (95% CI 9·1%-11·5%). Other mortality risk factors were younger age (either 2-5 months (aOR 9·94, 95% CI 6·67-14·84) or 6-11 months (aOR 2·67, 95% CI 1·71-4·16)), moderate malnutrition (aOR 2·41, 95% CI 1·87-3·09), and female sex (aOR 1·82, 95% CI 1·43-2·32). CONCLUSIONS: Children with a pulse oximetry measurement had a lower CFR. Many children hospitalized with chest indrawing pneumonia were hypoxemic and one in ten died. Young age and moderate malnutrition were risk factors for in-hospital chest indrawing pneumonia-related mortality. Pulse oximetry should be integrated in under-five pneumonia hospital care. |
Prospective association of daily steps with cardiovascular disease: A harmonized meta-analysis
Paluch AE , Bajpai S , Ballin M , Bassett DR , Buford TW , Carnethon MR , Chernofsky A , Dooley EE , Ekelund U , Evenson KR , Galuska DA , Jefferis BJ , Kong L , Kraus WE , Larson MG , Lee IM , Matthews CE , Newton RL Jr , Nordström A , Nordström P , Palta P , Patel AV , Pettee Gabriel K , Pieper CF , Pompeii L , Rees-Punia E , Spartano NL , Vasan RS , Whincup PH , Yang S , Fulton JE . Circulation 2022 147 (2) 122-131 BACKGROUND: Taking fewer than the widely promoted "10 000 steps per day" has recently been associated with lower risk of all-cause mortality. The relationship of steps and cardiovascular disease (CVD) risk remains poorly described. A meta-analysis examining the dose-response relationship between steps per day and CVD can help inform clinical and public health guidelines. METHODS: Eight prospective studies (20 152 adults [ie, ≥18 years of age]) were included with device-measured steps and participants followed for CVD events. Studies quantified steps per day and CVD events were defined as fatal and nonfatal coronary heart disease, stroke, and heart failure. Cox proportional hazards regression analyses were completed using study-specific quartiles and hazard ratios (HR) and 95% CI were meta-analyzed with inverse-variance-weighted random effects models. RESULTS: The mean age of participants was 63.2±12.4 years and 52% were women. The mean follow-up was 6.2 years (123 209 person-years), with a total of 1523 CVD events (12.4 per 1000 participant-years) reported. There was a significant difference in the association of steps per day and CVD between older (ie, ≥60 years of age) and younger adults (ie, <60 years of age). For older adults, the HR for quartile 2 was 0.80 (95% CI, 0.69 to 0.93), 0.62 for quartile 3 (95% CI, 0.52 to 0.74), and 0.51 for quartile 4 (95% CI, 0.41 to 0.63) compared with the lowest quartile. For younger adults, the HR for quartile 2 was 0.79 (95% CI, 0.46 to 1.35), 0.90 for quartile 3 (95% CI, 0.64 to 1.25), and 0.95 for quartile 4 (95% CI, 0.61 to 1.48) compared with the lowest quartile. Restricted cubic splines demonstrated a nonlinear association whereby more steps were associated with decreased risk of CVD among older adults. CONCLUSIONS: For older adults, taking more daily steps was associated with a progressively decreased risk of CVD. Monitoring and promoting steps per day is a simple metric for clinician-patient communication and population health to reduce the risk of CVD. |
Pancreatic cancer survival trends in the US from 2001 to 2014: a CONCORD-3 study
Nikšić M , Minicozzi P , Weir HK , Zimmerman H , Schymura MJ , Rees JR , Coleman MP , Allemani C . Cancer Commun (Lond) 2022 43 (1) 87-99 BACKGROUND: Survival from pancreatic cancer is low worldwide. In the US, the 5-year relative survival has been slightly higher for women, whites and younger patients than for their counterparts, and differences in age and stage at diagnosis may contribute to this pattern. We aimed to examine trends in survival by race, stage, age and sex for adults (15-99 years) diagnosed with pancreatic cancer in the US. METHODS: This population-based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001-2014, with follow-up to December 31, 2014. We estimated age-specific and age-standardized net survival at 1 and 5 years. RESULTS: Overall, 12.3% of patients were blacks, and 84.2% were whites. About 9.5% of patients were diagnosed with localized disease, but 50.5% were diagnosed at an advanced stage; slightly more among blacks, mainly among men. No substantial changes were seen over time (2001-2003, 2004-2008, 2009-2014). In general, 1-year net survival was higher in whites than in blacks (26.1% vs. 22.1% during 2001-2003, 35.1% vs. 31.4% during 2009-2014). This difference was particularly evident among patients with localized disease (49.6% in whites vs. 44.6% in blacks during 2001-2003, 60.1% vs. 55.3% during 2009-2014). The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis, and it widened over time (from 24.0% vs. 21.3% during 2001-2003 to 39.7% vs. 31.0% during 2009-2014). The survival gap was wider among men than among women. CONCLUSIONS: Gaps in 1- and 5-year survival between blacks and whites were persistent throughout 2001-2014, especially for patients diagnosed with a localized tumor, for which surgery is currently the only treatment modality with the potential for cure. |
Integrated Quantitative Targeted Lipidomics and Proteomics Reveal Unique Fingerprints of Multiple Metabolic Conditions.
Ivanova AA , Rees JC , Parks BA , Andrews M , Gardner M , Grigorutsa E , Kuklenyik Z , Pirkle JL , Barr JR . Biomolecules 2022 12 (10) Aberrations in lipid and lipoprotein metabolic pathways can lead to numerous diseases, including cardiovascular disease, diabetes, neurological disorders, and cancer. The integration of quantitative lipid and lipoprotein profiling of human plasma may provide a powerful approach to inform early disease diagnosis and prevention. In this study, we leveraged data-driven quantitative targeted lipidomics and proteomics to identify specific molecular changes associated with different metabolic risk categories, including hyperlipidemic, hypercholesterolemic, hypertriglyceridemic, hyperglycemic, and normolipidemic conditions. Based on the quantitative characterization of serum samples from 146 individuals, we have determined individual lipid species and proteins that were significantly up- or down-regulated relative to the normolipidemic group. Then, we established protein-lipid topological networks for each metabolic category and linked dysregulated proteins and lipids with defined metabolic pathways. To evaluate the differentiating power of integrated lipidomics and proteomics data, we have built an artificial neural network model that simultaneously and accurately categorized the samples from each metabolic risk category based on the determined lipidomics and proteomics profiles. Together, our findings provide new insights into molecular changes associated with metabolic risk conditions, suggest new condition-specific associations between apolipoproteins and lipids, and may inform new biomarker discovery in lipid metabolism-associated disorders. |
Prioritizing health care strategies to reduce childhood mortality
Madewell ZJ , Whitney CG , Velaphi S , Mutevedzi P , Mahtab S , Madhi SA , Fritz A , Swaray-Deen A , Sesay T , Ogbuanu IU , Mannah MT , Xerinda EG , Sitoe A , Mandomando I , Bassat Q , Ajanovic S , Tapia MD , Sow SO , Mehta A , Kotloff KL , Keita AM , Tippett Barr BA , Onyango D , Oele E , Igunza KA , Agaya J , Akelo V , Scott JAG , Madrid L , Kelil YE , Dufera T , Assefa N , Gurley ES , El Arifeen S , Spotts Whitney EA , Seib K , Rees CA , Blau DM . JAMA Netw Open 2022 5 (10) e2237689 IMPORTANCE: Although child mortality trends have decreased worldwide, deaths among children younger than 5 years of age remain high and disproportionately circumscribed to sub-Saharan Africa and Southern Asia. Tailored and innovative approaches are needed to increase access, coverage, and quality of child health care services to reduce mortality, but an understanding of health system deficiencies that may have the greatest impact on mortality among children younger than 5 years is lacking. OBJECTIVE: To investigate which health care and public health improvements could have prevented the most stillbirths and deaths in children younger than 5 years using data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used longitudinal, population-based, and mortality surveillance data collected by CHAMPS to understand preventable causes of death. Overall, 3390 eligible deaths across all 7 CHAMPS sites (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) between December 9, 2016, and December 31, 2021 (1190 stillbirths, 1340 neonatal deaths, 860 infant and child deaths), were included. Deaths were investigated using minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and fluids. MAIN OUTCOMES AND MEASURES: For each death, an expert multidisciplinary panel reviewed case data to determine the plausible pathway and causes of death. If the death was deemed preventable, the panel identified which of 10 predetermined health system gaps could have prevented the death. The health system improvements that could have prevented the most deaths were evaluated for each age group: stillbirths, neonatal deaths (aged <28 days), and infant and child deaths (aged 1 month to <5 years). RESULTS: Of 3390 deaths, 1505 (44.4%) were female and 1880 (55.5%) were male; sex was not recorded for 5 deaths. Of all deaths, 3045 (89.8%) occurred in a healthcare facility and 344 (11.9%) in the community. Overall, 2607 (76.9%) were deemed potentially preventable: 883 of 1190 stillbirths (74.2%), 1010 of 1340 neonatal deaths (75.4%), and 714 of 860 infant and child deaths (83.0%). Recommended measures to prevent deaths were improvements in antenatal and obstetric care (recommended for 588 of 1190 stillbirths [49.4%], 496 of 1340 neonatal deaths [37.0%]), clinical management and quality of care (stillbirths, 280 [23.5%]; neonates, 498 [37.2%]; infants and children, 393 of 860 [45.7%]), health-seeking behavior (infants and children, 237 [27.6%]), and health education (infants and children, 262 [30.5%]). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, interventions prioritizing antenatal, intrapartum, and postnatal care could have prevented the most deaths among children younger than 5 years because 75% of deaths among children younger than 5 were stillbirths and neonatal deaths. Measures to reduce mortality in this population should prioritize improving existing systems, such as better access to antenatal care, implementation of standardized clinical protocols, and public education campaigns. |
Derivation and validation of a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality in 20 countries
Rees CA , Colbourn T , Hooli S , King C , Lufesi N , McCollum ED , Mwansambo C , Cutland C , Madhi SA , Nunes M , Matthew JL , Addo-Yobo E , Chisaka N , Hassan M , Hibberd PL , Jeena PM , Lozano JM , MacLeod WB , Patel A , Thea DM , Nguyen NTV , Kartasasmita CB , Lucero M , Awasthi S , Bavdekar A , Chou M , Nymadawa P , Pape JW , Paranhos-Baccala G , Picot VS , Rakoto-Andrianarivelo M , Rouzier V , Russomando G , Sylla M , Vanhems P , Wang J , Asghar R , Banajeh S , Iqbal I , Maulen-Radovan I , Mino-Leon G , Saha SK , Santosham M , Singhi S , Basnet S , Strand TA , Bhatnagar S , Wadhwa N , Lodha R , Aneja S , Clara AW , Campbell H , Nair H , Falconer J , Qazi SA , Nisar YB , Neuman MI . BMJ Glob Health 2022 7 (4) INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings. METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for each candidate variable and assigned weighted points to derive the Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) risk assessment tool. We used bootstrapped selection with 200 repetitions to internally validate the PREPARE risk assessment tool. RESULTS: A total of 27 388 children were included in the analysis (mean age 14.0 months, pneumonia-related case fatality ratio 3.1%). The PREPARE risk assessment tool included patient age, sex, weight-for-age z-score, body temperature, respiratory rate, unconsciousness or decreased level of consciousness, convulsions, cyanosis and hypoxaemia at baseline. The PREPARE risk assessment tool had good discriminatory value when internally validated (area under the curve 0.83, 95% CI 0.81 to 0.84). CONCLUSIONS: The PREPARE risk assessment tool had good discriminatory ability for identifying children at risk of hospitalised pneumonia-related mortality in a large, geographically diverse dataset. After external validation, this tool may be implemented in various settings to identify children at risk of hospitalised pneumonia-related mortality. |
The small HDL particle hypothesis of Alzheimer's disease
Martinez AE , Weissberger G , Kuklenyik Z , He X , Meuret C , Parekh T , Rees JC , Parks BA , Gardner MS , King SM , Collier TS , Harrington MG , Sweeney MD , Wang X , Zlokovic BV , Joe E , Nation DA , Schneider LS , Chui HC , Barr JR , Han SD , Krauss RM , Yassine HN . Alzheimers Dement 2022 19 (2) 391-404 We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes. |
Daily steps and all-cause mortality: a meta-analysis of 15 international cohorts
Paluch AE , Bajpai S , Bassett DR , Carnethon MR , Ekelund U , Evenson KR , Galuska DA , Jefferis BJ , Kraus WE , Lee IM , Matthews CE , Omura JD , Patel AV , Pieper CF , Rees-Punia E , Dallmeier D , Klenk J , Whincup PH , Dooley EE , PetteeGabriel K , Palta P , Pompeii LA , Chernofsky A , Larson MG , Vasan RS , Spartano N , Ballin M , Nordstrm P , Nordstrm A , Anderssen SA , Hansen BH , Cochrane JA , Dwyer T , Wang J , Ferrucci L , Liu F , Schrack J , Urbanek J , Saint-Maurice PF , Yamamoto N , Yoshitake Y , Newton RLJr , Yang S , Shiroma EJ , Fulton JE . Lancet Public Health 2022 7 (3) e219-e228 BACKGROUND: Although 10000 steps per day is widely promoted to have health benefits, there is little evidence to support this recommendation. We aimed to determine the association between number of steps per day and stepping rate with all-cause mortality. METHODS: In this meta-analysis, we identified studies investigating the effect of daily step count on all-cause mortality in adults (aged 18 years), via a previously published systematic review and expert knowledge of the field. We asked participating study investigators to process their participant-level data following a standardised protocol. The primary outcome was all-cause mortality collected from death certificates and country registries. We analysed the dose-response association of steps per day and stepping rate with all-cause mortality. We did Cox proportional hazards regression analyses using study-specific quartiles of steps per day and calculated hazard ratios (HRs) with inverse-variance weighted random effects models. FINDINGS: We identified 15 studies, of which seven were published and eight were unpublished, with study start dates between 1999 and 2018. The total sample included 47471 adults, among whom there were 3013 deaths (101 per 1000 participant-years) over a median follow-up of 71 years ([IQR 43-99]; total sum of follow-up across studies was 297837 person-years). Quartile median steps per day were 3553 for quartile 1, 5801 for quartile 2, 7842 for quartile 3, and 10901 for quartile 4. Compared with the lowest quartile, the adjusted HR for all-cause mortality was 060 (95% CI 051-071) for quartile 2, 055 (049-062) for quartile 3, and 047 (039-057) for quartile 4. Restricted cubic splines showed progressively decreasing risk of mortality among adults aged 60 years and older with increasing number of steps per day until 6000-8000 steps per day and among adults younger than 60 years until 8000-10000 steps per day. Adjusting for number of steps per day, comparing quartile 1 with quartile 4, the association between higher stepping rates and mortality was attenuated but remained significant for a peak of 30 min (HR 067 [95% CI 056-083]) and a peak of 60 min (067 [050-090]), but not significant for time (min per day) spent walking at 40 steps per min or faster (112 [096-132]) and 100 steps per min or faster (086 [058-128]). INTERPRETATION: Taking more steps per day was associated with a progressively lower risk of all-cause mortality, up to a level that varied by age. The findings from this meta-analysis can be used to inform step guidelines for public health promotion of physical activity. FUNDING: US Centers for Disease Control and Prevention. |
Incidence of herpes simplex virus type 2 infection among African women using depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: a nested randomized trial
Mugo NR , Stalter RM , Heffron R , Rees H , Scoville CW , Morrison C , Kourtis AP , Bukusi E , Beksinka M , Philip NM , Beesham I , Deese J , Edward V , Donnell D , Baeten JM . Clin Infect Dis 2021 75 (4) 586-595 BACKGROUND: Globally, women have higher herpes simplex type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of intramuscular depot medroxyprogesterone acetate (DMPA-IM). METHODS: Within a randomized trial of the effect of three contraceptive methods - DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant - on HIV acquisition, we assessed HSV-2 acquisition. HSV-2 and HIV seronegative women, aged 16-35 years, and seeking effective contraception were followed for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015-2018. HSV-2 serologic testing was done at enrollment and final study visits. Intention-to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method. FINDINGS: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI] 0.65-0.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI 0.71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI 0.89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55, 95% CI 2.78-4.48). INTERPRETATION: In a randomized trial, we found no association between HSV-2 acquisition and use of three contraceptive methods. |
Trends in short-term survival from distant-stage cutaneous melanoma in the United States, 2001-2013 (CONCORD-3)
Di Carlo V , Estève J , Johnson C , Girardi F , Weir HK , Wilson RJ , Minicozzi P , Cress RD , Lynch CF , Pawlish KS , Rees JR , Coleman MP , Allemani C . JNCI Cancer Spectr 2020 4 (6) pkaa078 BACKGROUND: Survival from metastatic cutaneous melanoma is substantially lower than for localized disease. Treatments for metastatic melanoma have been limited, but remarkable clinical improvements have been reported in clinical trials in the last decade. We described the characteristics of US patients diagnosed with cutaneous melanoma during 2001-2013 and assessed trends in short-term survival for distant-stage disease. METHODS: Trends in 1-year net survival were estimated using the Pohar Perme estimator, controlling for background mortality with life tables of all-cause mortality rates by county of residence, single year of age, sex, and race for each year 2001-2013. We fitted a flexible parametric survival model on the log-hazard scale to estimate the effect of race on the hazard of death because of melanoma and estimated 1-year net survival by race. RESULTS: Only 4.4% of the 425 915 melanomas were diagnosed at a distant stage, cases diagnosed at a distant stage are more commonly men, older patients, and African Americans. Age-standardized, 1-year net survival for distant-stage disease was stable at approximately 43% during 2001-2010. From 2010 onward, survival improved rapidly, reaching 58.9% (95% confidence interval = 56.6% to 61.2%) for patients diagnosed in 2013. Younger patients experienced the largest improvement. Survival for distant-stage disease increased in both Blacks and Whites but was consistently lower in Blacks. CONCLUSIONS: One-year survival for distant-stage melanoma improved during 2001-2013, particularly in younger patients and those diagnosed since 2010. This improvement may be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. Persistent survival inequalities exist between Blacks and Whites, suggesting differential access to treatment. |
A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool
Billingsley P , Binka F , Chaccour C , Foy B , Gold S , Gonzalez-Silva M , Jacobson J , Jagoe G , Jones C , Kachur P , Kobylinski K , Last A , Lavery JV , Mabey D , Mboera D , Mbogo C , Mendez-Lopez A , Rabinovich NR , Rees S , Richards F , Rist C , Rockwood J , Ruiz-Castillo P , Sattabongkot J , Saute F , Slater H , Steer A , Xia K , Zullinger R . Am J Trop Med Hyg 2020 102 3-24 In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of Anopheles mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease. |
Impact of Plasmodium falciparum gene deletions on malaria rapid diagnostic test performance.
Gatton ML , Chaudhry A , Glenn J , Wilson S , Ah Y , Kong A , Ord RL , Rees-Channer RR , Chiodini P , Incardona S , Cheng Q , Aidoo M , Cunningham J . Malar J 2020 19 (1) 392 BACKGROUND: Malaria rapid diagnostic tests (RDTs) have greatly improved access to diagnosis in endemic countries. Most RDTs detect Plasmodium falciparum histidine-rich protein 2 (HRP2), but their sensitivity is seriously threatened by the emergence of pfhrp2-deleted parasites. RDTs detecting P. falciparum or pan-lactate dehydrogenase (Pf- or pan-LDH) provide alternatives. The objective of this study was to systematically assess the performance of malaria RDTs against well-characterized pfhrp2-deleted P. falciparum parasites. METHODS: Thirty-two RDTs were tested against 100 wild-type clinical isolates (200 parasites/µL), and 40 samples from 10 culture-adapted and clinical isolates of pfhrp2-deleted parasites. Wild-type and pfhrp2-deleted parasites had comparable Pf-LDH concentrations. Pf-LDH-detecting RDTs were also tested against 18 clinical isolates at higher density (2,000 parasites/µL) lacking both pfhrp2 and pfhrp3. RESULTS: RDT positivity against pfhrp2-deleted parasites was highest (> 94%) for the two pan-LDH-only RDTs. The positivity rate for the nine Pf-LDH-detecting RDTs varied widely, with similar median positivity between double-deleted (pfhrp2/3 negative; 63.9%) and single-deleted (pfhrp2-negative/pfhrp3-positive; 59.1%) parasites, both lower than against wild-type P. falciparum (93.8%). Median positivity for HRP2-detecting RDTs against 22 single-deleted parasites was 69.9 and 35.2% for HRP2-only and HRP2-combination RDTs, respectively, compared to 96.0 and 92.5% for wild-type parasites. Eight of nine Pf-LDH RDTs detected all clinical, double-deleted samples at 2,000 parasites/µL. CONCLUSIONS: The pan-LDH-only RDTs evaluated performed well. Performance of Pf-LDH-detecting RDTs against wild-type P. falciparum does not necessarily predict performance against pfhrp2-deleted parasites. Furthermore, many, but not all HRP2-based RDTs, detect pfhrp2-negative/pfhrp3-positive samples, with implications for the HRP2-based RDT screening approach for detection and surveillance of HRP2-negative parasites. |
Global vaccine action plan lessons learned I: Recommendations for the next decade
MacDonald N , Mohsni E , Al-Mazrou Y , Kim Andrus J , Arora N , Elden S , Madrid MY , Martin R , Mahmoud Mustafa A , Rees H , Salisbury D , Zhao Q , Jones I , Steffen CA , Hombach J , O'Brien KL , Cravioto A . Vaccine 2020 38 (33) 5364-5371 The Global Vaccine Action Plan 2011-2020 (GVAP) was developed to realize the ambitions of the Decade of Vaccines - that all individuals and communities enjoy lives free from vaccine-preventable diseases. It included a comprehensive monitoring and evaluation/accountability framework to assess progress towards global targets with recommendations for corrective actions. While many of the GVAP targets are very unlikely to be met by the end of 2020, substantial progress has nevertheless been made, establishing a strong foundation for a successor global immunization strategy, the Immunization Agenda 2030 (IA2030). The Strategic Advisory Group of Experts on immunization has made a series of recommendations to ensure that the lessons learned from GVAP inform the development and implementation of IA2030. |
A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis.
Justice CM , Cuellar A , Bala K , Sabourin JA , Cunningham ML , Crawford K , Phipps JM , Zhou Y , Cilliers D , Byren JC , Johnson D , Wall SA , Morton JEV , Noons P , Sweeney E , Weber A , Rees KEM , Wilson LC , Simeonov E , Kaneva R , Yaneva N , Georgiev K , Bussarsky A , Senders C , Zwienenberg M , Boggan J , Roscioli T , Tamburrini G , Barba M , Conway K , Sheffield VC , Brody L , Mills JL , Kay D , Sicko RJ , Langlois PH , Tittle RK , Botto LD , Jenkins MM , LaSalle JM , Lattanzi W , Wilkie AOM , Wilson AF , Romitti PA , Boyadjiev SA . Hum Genet 2020 139 (8) 1077-1090 Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P </= 5 x 10(-8)): rs781716 (P = 4.71 x 10(-9); odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 x 10(-8); OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 x 10(-9); OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 x 10(-8), OR = 0.45; P = 3.31 x 10(-8), OR = 0.45; P = 1.09 x 10(-8), OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 x 10(-8), OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 x 10(-6)). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821-55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS. |
Breast and colorectal cancer recurrence and progression captured by five U.S. population-based registries: Findings from National Program of Cancer Registries patient-centered outcome research
Thompson TD , Pollack LA , Johnson CJ , Wu XC , Rees JR , Hsieh MC , Rycroft R , Culp M , Wilson R , Wu M , Zhang K , Benard V . Cancer Epidemiol 2020 64 101653 OBJECTIVES: Cancer recurrence is a meaningful patient outcome that is not captured in population-based cancer surveillance. This project supported National Program of Cancer Registries central cancer registries in five U.S. states to determine the disease course of all breast and colorectal cancer cases. The aims were to assess the feasibility of capturing disease-free (DF) status and subsequent cancer outcomes and to explore analytic approaches for future studies. METHODS: Data were obtained on 11,769 breast and 6033 colorectal cancer cancers diagnosed in 2011. Registry-trained abstractors reviewed medical records from multiple sources for up to 60 months to determine documented DF status, recurrence, progression and residual disease. We described the occurrence of these patient-centered outcomes along with analytic considerations when determining time-to-event outcomes and recurrence-free survival. RESULTS: Disease-free status was determined on all but 3.8 % of cancer cases. Among 14,458 cases that became DF, 6.1 % of breast and 13.0 % of colorectal cancer cases had a documented recurrence. Recurrence-free survival varied by stage; for stage II-III cancers at 48 months, 83.2 % of female breast and 69.2 % of colorectal cancer patients were alive without recurrence. The ability to distinguish between progression and residual disease among never disease-free patients limited our ability to examine progression as an outcome. CONCLUSIONS: This study demonstrated that population-based registries given intense support and resources can capture recurrence and offer a generalizable picture of cancer outcomes. Further work on refining definitions, sampling strategies, and novel approaches to capture recurrence could advance the ability of a national cancer surveillance system to contribute to patient-centered outcomes research. |
Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI
Blount BC , Karwowski MP , Shields PG , Morel-Espinosa M , Valentin-Blasini L , Gardner M , Braselton M , Brosius CR , Caron KT , Chambers D , Corstvet J , Cowan E , De Jesus VR , Espinosa P , Fernandez C , Holder C , Kuklenyik Z , Kusovschi JD , Newman C , Reis GB , Rees J , Reese C , Silva L , Seyler T , Song MA , Sosnoff C , Spitzer CR , Tevis D , Wang L , Watson C , Wewers MD , Xia B , Heitkemper DT , Ghinai I , Layden J , Briss P , King BA , Delaney LJ , Jones CM , Baldwin GT , Patel A , Meaney-Delman D , Rose D , Krishnasamy V , Barr JR , Thomas J , Pirkle JL . N Engl J Med 2019 382 (8) 697-705 BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.). |
A review of the WHO malaria rapid diagnostic test product testing programme (2008-2018): performance, procurement and policy
Cunningham J , Jones S , Gatton ML , Barnwell JW , Cheng Q , Chiodini PL , Glenn J , Incardona S , Kosack C , Luchavez J , Menard D , Nhem S , Oyibo W , Rees-Channer RR , Gonzalez I , Bell D . Malar J 2019 18 (1) 387 Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics. |
Evaluation of bronchoalveolar lavage fluid from patients in an outbreak of e-cigarette, or vaping, product use-associated lung injury - 10 states, August-October 2019
Blount BC , Karwowski MP , Morel-Espinosa M , Rees J , Sosnoff C , Cowan E , Gardner M , Wang L , Valentin-Blasini L , Silva L , De Jesus VR , Kuklenyik Z , Watson C , Seyler T , Xia B , Chambers D , Briss P , King BA , Delaney L , Jones CM , Baldwin GT , Barr JR , Thomas J , Pirkle JL . MMWR Morb Mortal Wkly Rep 2019 68 (45) 1040-1041 CDC, the Food and Drug Administration (FDA), state and local health departments, and multiple public health and clinical partners are investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). Based on data collected as of October 15, 2019, 86% of 867 EVALI patients reported using tetrahydrocannabinol (THC)-containing products in the 3 months preceding symptom onset (1). Analyses of THC-containing product samples by FDA and state public health laboratories have identified potentially harmful constituents in these products, such as vitamin E acetate, medium chain triglyceride oil (MCT oil), and other lipids (2,3) (personal communication, D.T. Heitkemper, FDA Forensic Chemistry Center, November 2019). Vitamin E acetate, in particular, might be used as an additive in the production of e-cigarette, or vaping, products; it also can be used as a thickening agent in THC products (4). Inhalation of vitamin E acetate might impair lung function (5-7). |
Development and application of a high throughput one-pot extraction protocol for quantitative LC-MS/MS analysis of phospholipids in serum and lipoprotein fractions in normolipidemic and dyslipidemic subjects
Gardner MS , Kuklenyik Z , Lehtikoski A , Carter KA , McWilliams LG , Kusovschi J , Bierbaum K , Jones JI , Rees J , Reis G , Pirkle JL , Barr JR . J Chromatogr B Analyt Technol Biomed Life Sci 2019 1118-1119 137-147 Progress toward better diagnosis and treatment of lipid metabolism-related diseases requires high throughput approaches for multiplexed quantitative analysis of structurally diverse lipids, including phospholipids (PLs). This work demonstrates a simplified "one-pot" phospholipid extraction protocol, as an alternative to conventional liquid-liquid extraction. Performed in a 96-well format, the extraction was coupled with high throughput UPLC and multiplexed tandem mass spectrometry (MS/MS) detection, allowing non-targeted quantification of phosphatidylcholines (PC), sphingomyelins (SM), lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE), and phosphatidylinositols (PI). Using 50muL aliquots of serum samples from 110 individuals, lipoproteins were fractionated by size, and analyzed for phospholipids and non-polar lipids including free cholesterol (FC), cholesteryl esters (CEs) and triglycerides (TGs). Analysis of serum samples with wide range of Total-TG levels showed significant differences in PL composition. The correlations of molar ratios in lipoprotein size fractions, SM/PL with FC/PL, PE/PL with TG/CE, and PE/PL with PI/PL, demonstrate the applicability of the method for quantitative composition analysis of high, low and very-low density lipoproteins (HDL, LDL and VLDL), and characterization of lipid metabolism related disease states. |
Core lipid, surface lipid and apolipoprotein composition analysis of lipoprotein particles as a function of particle size in one workflow integrating asymmetric flow field-flow fractionation and liquid chromatography-tandem mass spectrometry
Kuklenyik Z , Jones JI , Gardner MS , Schieltz DM , Parks BA , Toth CA , Rees JC , Andrews ML , Carter K , Lehtikoski AK , McWilliams LG , Williamson YM , Bierbaum KP , Pirkle JL , Barr JR . PLoS One 2018 13 (4) e0194797 Lipoproteins are complex molecular assemblies that are key participants in the intricate cascade of extracellular lipid metabolism with important consequences in the formation of atherosclerotic lesions and the development of cardiovascular disease. Multiplexed mass spectrometry (MS) techniques have substantially improved the ability to characterize the composition of lipoproteins. However, these advanced MS techniques are limited by traditional pre-analytical fractionation techniques that compromise the structural integrity of lipoprotein particles during separation from serum or plasma. In this work, we applied a highly effective and gentle hydrodynamic size based fractionation technique, asymmetric flow field-flow fractionation (AF4), and integrated it into a comprehensive tandem mass spectrometry based workflow that was used for the measurement of apolipoproteins (apos A-I, A-II, A-IV, B, C-I, C-II, C-III and E), free cholesterol (FC), cholesterol esters (CE), triglycerides (TG), and phospholipids (PL) (phosphatidylcholine (PC), sphingomyelin (SM), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and lysophosphatidylcholine (LPC)). Hydrodynamic size in each of 40 size fractions separated by AF4 was measured by dynamic light scattering. Measuring all major lipids and apolipoproteins in each size fraction and in the whole serum, using total of 0.1 ml, allowed the volumetric calculation of lipoprotein particle numbers and expression of composition in molar analyte per particle number ratios. Measurements in 110 serum samples showed substantive differences between size fractions of HDL and LDL. Lipoprotein composition within size fractions was expressed in molar ratios of analytes (A-I/A-II, C-II/C-I, C-II/C-III. E/C-III, FC/PL, SM/PL, PE/PL, and PI/PL), showing differences in sample categories with combinations of normal and high levels of Total-C and/or Total-TG. The agreement with previous studies indirectly validates the AF4-LC-MS/MS approach and demonstrates the potential of this workflow for characterization of lipoprotein composition in clinical studies using small volumes of archived frozen samples. |
Capture of tobacco use among population-based registries: Findings from 10 National Program of Cancer Registries states
Siegel DA , Henley SJ , Wike JM , Ryerson AB , Johnson CJ , Rees JR , Pollack LA . Cancer 2018 124 (11) 2381-2389 BACKGROUND: Tobacco use data are important when the epidemiology and prognosis of tobacco-associated cancers are being defined. Central cancer registries in 10 National Program of Cancer Registries states pilot-tested the collection of standardized tobacco use variables. This study evaluated the capture of tobacco use data and examined smoking prevalence among cancer patients. METHODS: Participating registries collected data about the use of tobacco-cigarettes, other smoked tobacco, and smokeless tobacco-for cases diagnosed during 2011-2013. The percentage of cases with known tobacco variable values was calculated, and the prevalence of tobacco use was analyzed by the primary cancer site and state. RESULTS: Among 1,646,505 incident cancer cases, 51% had known cigarette use data: 18% were current users, 31% were former users, and 51% reported never using. The percentage of cases with a known status for both other smoked tobacco and smokeless tobacco was 43%, with 97% and 98% coded as never users, respectively. The percent known for cigarette use ranged from 27% to 81% by state and improved from 47% in 2011 to 59% in 2013 for all 10 states combined. The percent known for cigarette use and the prevalence of ever smoking cigarettes were highest for laryngeal cancer and tracheal, lung, and bronchus cancer. CONCLUSIONS: Cancer registrars ascertained cigarette use for slightly more than half of all new cancer cases, but other tobacco-related fields were less complete. Studies to evaluate the validity of specific tobacco-related variables and the ability of cancer registries to capture this information from the medical record are needed to gauge the usefulness of collecting these variables through cancer surveillance systems. Cancer 2018. (c) 2018 American Cancer Society. |
Concordance of self-reported hormonal contraceptive use and presence of exogenous hormones in serum among African women
Pyra M , Lingappa JR , Heffron R , Erikson DW , Blue SW , Patel RC , Nanda K , Rees H , Mugo NR , Davis NL , Kourtis AP , Baeten JM . Contraception 2018 97 (4) 357-362 OBJECTIVES: Studies that rely on self-report to investigate the relationship between hormonal contraceptive use and HIV acquisition and transmission, as well as other health outcomes, could have compromised results due to misreporting. We determined the frequency of misreported hormonal contraceptive use among African women with and at risk for HIV. STUDY DESIGN: We tested 1102 archived serum samples from 664 African women who had participated in prospective HIV prevention studies. Using a novel high-performance liquid chromatography mass-spectrometry assay, we quantified exogenous hormones for injectables (medroxyprogesterone acetate or norethisterone), oral contraceptives (OC) (levonorgestrel or ethinyl estradiol), and implants (levonorgestrel or etonogestrel) and compared them to self-reported use. RESULTS: Among women reporting hormonal contraceptive use, 258/358 (72%) of samples were fully concordant with self-report, as were 642/744 (86%) of samples from women reporting no hormonal contraceptive use. However, 42/253 (17%) of samples from women reporting injectable use, 41/66 (62%) of samples from self-reported OC users, and 3/39 (8%) of samples from self-reported implant users had no quantifiable hormones. Among self-reported non-users, 102/744 (14%) had>/=1 hormone present. Concordance between self-reported method and exogenous hormones did not differ by HIV status. CONCLUSION: Among African women with and at risk for HIV, testing of exogenous hormones revealed agreement with self-reported contraceptive use for most women. However, unexpected exogenous hormones were identified among self-reported hormonal contraceptive users and non-users, and an important fraction of women reporting hormonal contraceptive use had no hormones detected; absence of oral contraceptive hormones could be due, at least in part, to samples taken during the hormone-free interval. Misreporting of hormonal contraceptive use could lead to biased results in observational studies of the relationship between contraceptive use and health outcomes. IMPLICATIONS: Research studies investigating associations between hormonal contraceptive use and HIV should consider validating self-reported use by objective measures; because both over- and under-reporting of use occurs, potential misclassification based on self-report could lead to biased results in directions that cannot be easily predicted. |
Surfaceome Analysis Protocol for the Identification of Novel Bordetella pertussis Antigens.
Williamson YM , Whitmon J , West-Deadwyler R , Moura H , Woolfitt AR , Rees J , Schieltz DM , Barr JR . Methods Mol Biol 2018 1722 3-20 The bacterial surfaceome, comprising outer membrane-sorted and/or associated (i.e., cell transporters), cell surface-exposed (i.e., adhesins) and extracellularly secreted proteins (i.e., toxins), has been characterized in bacterial pathogens, such as Bordetella pertussis (Bp) to provide information for use in development of diagnostic and prevention strategies. This protein subset has clinical significance, as these bacterial proteins are often associated with attachment to host cells, microbial pathogenesis and antibody-mediated immunity. Here we describe classical surface membrane protein enrichment techniques, followed by proteomic methodologies, such as gel-free protein separation and antibody-affinity capture technologies in combination with nano-liquid chromatography mass spectrometry, for the identification and characterization of Bp surfaceome proteins. |
Harmonizing lipidomics: NIST interlaboratory comparison exercise for lipidomics using Standard Reference Material 1950 metabolites in frozen human plasma
Bowden JA , Heckert A , Ulmer CZ , Jones CM , Koelmel JP , Abdullah L , Ahonen L , Alnouti Y , Armando A , Asara JM , Bamba T , Barr JR , Bergquist J , Borchers CH , Brandsma J , Breitkopf SB , Cajka T , Cazenave-Gassiot A , Checa A , Cinel MA , Colas RA , Cremers S , Dennis EA , Evans JE , Fauland A , Fiehn O , Gardner MS , Garrett TJ , Gotlinger KH , Han J , Huang Y , Neo AH , Hyotylainen T , Izumi Y , Jiang H , Jiang H , Jiang J , Kachman M , Kiyonami R , Klavins K , Klose C , Kofeler HC , Kolmert J , Koal T , Koster G , Kuklenyik Z , Kurland IJ , Leadley M , Lin K , Maddipati KR , McDougall D , Meikle PJ , Mellett NA , Monnin C , Moseley MA , Nandakumar R , Oresic M , Patterson RE , Peake D , Pierce JS , Post M , Postle AD , Pugh R , Qui Y , Quehenberger O , Ramrup P , Rees J , Rembiesa B , Reynaud D , Roth MR , Sales S , Schuhmann K , Schwartzman ML , Serhan CN , Shevchenko A , Somerville SE , St John-Williams L , Surma MA , Takeda H , Thakare R , Thompson JW , Torta F , Triebl A , Trötzmüller M , Ubhayasekera SJK , Vuckovic D , Weir JM , Welti R , Wenk MR , Wheelock CE , Yao L , Yuan M , Zhao XH , Zhou S . J Lipid Res 2017 58 (12) 2275-2288 As the lipidomics field continues to advance, self-evaluation within the community is critical. Here, we performed an interlaboratory comparison exercise for lipidomics using Standard Reference Material (SRM) 1950 Metabolites in Frozen Human Plasma, a commercially available reference material. The interlaboratory study comprised 31 diverse laboratories, with each lab using a different lipidomics workflow. A total of 1527 unique lipids were measured across all laboratories, and consensus location estimates and associated uncertainties were determined for 339 of these lipids measured at the sum composition level by five or more participating laboratories. These evaluated lipids detected in SRM 1950 serve as community-wide benchmarks for intra- and inter-laboratory quality control and method validation. These analyses were performed using non-standardized laboratory-independent workflows. The consensus locations were also compared to a previous examination of SRM 1950 by the LIPID MAPS consortium. While the central theme of the interlaboratory study was to provide values to help harmonize lipids, lipid mediators, and precursor measurements across the community, it was also initiated to stimulate a discussion regarding areas in need of improvement. |
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