Publications by authors named "Abigail Ward"

22 Publications

  • Page 1 of 1

Factors associated with the decline of malaria in Myanmar's Ayeyarwady Region between 2013 and 2017.

Sci Rep 2021 Oct 14;11(1):20470. Epub 2021 Oct 14.

Myanmar Vector Borne Disease Control Program, Ministry of Health and Sports, Nay Pyi Taw, Myanmar.

The burden of malaria in Myanmar has declined rapidly in recent years; cases decreased from 333,871 in 2013 to 85,019 in 2017 (75% decrease). Decline of malaria in the Ayeyarwady Region of Myanmar reflects this trend with an 86% decrease in cases over this period. In this exploratory analysis, quantitative and qualitative information were assessed to explore potential factors responsible for the decline of malaria in Ayeyarwady. Data on malaria incidence, programmatic financing, surveillance, case management, vector control interventions, climate and ecological factors, and policies and guidelines spanning 2013 to 2017 were compiled. Poisson regression models that adjust for correlation were used to analyze the association between annual malaria case numbers with malaria intervention factors at the township level. Between 2013 and 2017, there was a decrease in mean township-level malaria incidence per 1000 from 3.03 (SD 4.59) to 0.34 (SD 0.79); this decline coincided with the implementation of the government's multi-pronged malaria elimination strategy, an increase of approximately 50.8 million USD in malaria funding nationally, and a period of deforestation in the region. Increased funding in Ayeyarwady was invested in interventions associated with the decline in caseload, and the important roles of surveillance and case management should be maintained while Myanmar works towards malaria elimination.
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http://dx.doi.org/10.1038/s41598-021-99737-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8516986PMC
October 2021

Education, Implementation, and Teams: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Resuscitation 2020 Nov 21;156:A188-A239. Epub 2020 Oct 21.

For this 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, the Education, Implementation, and Teams Task Force applied the population, intervention, comparator, outcome, study design, time frame format and performed 15 systematic reviews, applying the Grading of Recommendations, Assessment, Development, and Evaluation guidance. Furthermore, 4 scoping reviews and 7 evidence updates assessed any new evidence to determine if a change in any existing treatment recommendation was required. The topics covered included training for the treatment of opioid overdose; basic life support, including automated external defibrillator training; measuring implementation and performance in communities, and cardiac arrest centers; advanced life support training, including team and leadership training and rapid response teams; measuring cardiopulmonary resuscitation performance, feedback devices, and debriefing; and the use of social media to improve cardiopulmonary resuscitation application.
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http://dx.doi.org/10.1016/j.resuscitation.2020.09.014DOI Listing
November 2020

Text-only and picture conversation aids both supported shared decision making for breast cancer surgery: Analysis from a cluster randomized trial.

Patient Educ Couns 2020 11 28;103(11):2235-2243. Epub 2020 Jul 28.

The Dartmouth Institute for Health Policy & Clinical Practice, Dartmouth College, Lebanon, NH, USA. Electronic address:

Objectives: To determine if two encounter conversation aids for early-stage breast cancer surgery increased observed and patient-reported shared decision making (SDM) compared with usual care and if observed and patient-reported SDM were associated.

Methods: Surgeons in a cluster randomized trial at four cancer centers were randomized to use an Option Grid, Picture Option Grid, or usual care. We used bivariate statistics, linear regression, and multilevel models to evaluate the influence of trial arm, patient socioeconomic status and health literacy on observed SDM (via OPTION-5) and patient-reported SDM (via collaboRATE).

Results: From 311 recordings, OPTION-5 scores were 73/100 for Option Grid (n = 40), 56.3/100 for Picture Option Grid (n = 144), and 41.0/100 for usual care (n = 127; p < 0.0001). Top collaboRATE scores were 81.6 % for Option Grid, 80.0 % for Picture Option Grid, and 56.4 % for usual care (p < 0.001). Top collaboRATE scores correlated with an 8.60 point (95 %CI 0.66, 13.7) higher OPTION-5 score (p = 0.008) with no correlation in the multilevel analysis. Patients of lower socioeconomic status had lower OPTION-5 scores before accounting for clustering.

Conclusions: Both conversation aids led to meaningfully higher observed and patient-reported SDM. Observed and patient-reported SDM were not strongly correlated.

Practice Implications: Healthcare providers could implement these conversation aids in real-world settings.
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http://dx.doi.org/10.1016/j.pec.2020.07.015DOI Listing
November 2020

The optimal surface for delivery of CPR: A systematic review and meta-analysis.

Resuscitation 2020 10 2;155:159-164. Epub 2020 Aug 2.

University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK. Electronic address:

Aim: To determine the effect of CPR delivery surface (e.g. firm mattress, floor, backboard) on patient outcomes and CPR delivery.

Methods: We searched Medline, Cochrane Library and Web of Science for studies published since 2009 that evaluated the effect of CPR delivery surface in adults and children on patient outcomes and quality of CPR. We included randomised controlled trials only. We identified pre-2010 studies from the 2010 ILCOR evaluation of this topic. Two reviewers independently screened titles/ abstracts and full-text papers, extracted data and assessed risk of bias. Evidence certainty for each outcome was evaluated using GRADE methodology. Where appropriate, we pooled data in a meta-analysis, using a random-effects model.

Results: Database searches identified 2701 citations. We included seven studies published since 2009. We analysed these studies together with the four studies included in the previous ILCOR review. All included studies were randomised controlled trials in manikins. Certainty of evidence was very low. Increasing mattress stiffness or moving the manikin from the bed to the floor did not improve compression depth. Use of a backboard marginally improved compression depth (mean difference 3 mm (95% CI 1-4).

Conclusion: The use of a backboard led to a small increase in chest compression depth in manikin trials. Different mattress types or delivery of CPR on the floor did not affect chest compression depth. PROSPERO CRD42019154791.
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http://dx.doi.org/10.1016/j.resuscitation.2020.07.020DOI Listing
October 2020

Making the most of small samples: Optimization of tissue allocation of pediatric solid tumors for clinical and research use.

Pediatr Blood Cancer 2020 09 15;67(9):e28326. Epub 2020 Jul 15.

Department of Pathology, Boston Children's Hospital, Boston, Massachusetts.

Introduction: Tissue from pediatric solid tumors is in high demand for use in high-impact research studies, making the allocation of tissue from an anatomic pathology laboratory challenging. We designed, implemented, and assessed an interdepartmental process to optimize tissue allocation of pediatric solid tumors for both clinical care and research.

Methods: Oncologists, pathologists, surgeons, interventional radiologists, pathology technical staff, and clinical research coordinators participated in the workflow design. Procedures were created to address patient identification and consent, prioritization of protocols, electronic communication of requests, tissue preparation, and distribution. Pathologists were surveyed about the value of the new workflow.

Results: Over a 5-year period, 644 pediatric solid tumor patients consented to one or more studies requesting archival or fresh tissue. Patients had a variety of tumor types, with many rare and singular diagnoses. Sixty-seven percent of 1768 research requests were fulfilled. Requests for archival tissue were fulfilled at a significantly higher rate than those for fresh tissue (P > .001), and requests from resection specimens were fulfilled at a significantly higher rate than those from biopsies (P > .0001). In an anonymous survey, seven of seven pathologists reported that the process had improved since the introduction of the electronic communication model.

Conclusions: A collaborative and informed model for tissue allocation is successful in distributing archival and fresh tissue for clinical research studies. Our workflows and policies have gained pathologists' approval and streamlined our processes. As clinical and research programs evolve, a thoughtful tissue allocation process will facilitate ongoing research.
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http://dx.doi.org/10.1002/pbc.28326DOI Listing
September 2020

DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor.

Mod Pathol 2020 10 14;33(10):1910-1921. Epub 2020 Apr 14.

Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

The spectrum of neoplasms associated with DICER1 variants continues to expand, with the recent addition of primary "DICER1-associated central nervous system sarcoma" (DCS). DCS is a high-grade malignancy predominantly affecting pediatric patients. Six pediatric DCS were identified through a combination of clinical diagnostic studies, archival inquiry, and interinstitutional collaboration. Clinical, histologic, immunohistologic, and molecular features were examined. Genomic findings in the 6 DCS were compared with those in 14 additional DICER1-associated tumors sequenced with the same assay. The six patients presented at ages 3-15 years with CNS tumors located in the temporal (n = 2), parietal (n = 1), fronto-parietal (n = 1), and frontal (n = 2) lobes. All underwent surgical resection. Histologic examination demonstrated high-grade malignant spindle cell tumors with pleuropulmonary blastoma-like embryonic "organoid" features and focal rhabdomyoblastic differentiation; immature cartilage was seen in one case. Immunohistochemically, there was patchy desmin and myogenin staining, and patchy loss of H3K27me3, and within eosinophilic cytoplasmic globules, alfa-fetoprotein staining. Biallelic DICER1 variants were identified in all cases, with germline variants in two of five patients tested. DCS demonstrated genomic alterations enriched for Ras pathway activation and TP53 inactivation. Tumor mutational burden was significantly higher in the 6 DCS tumors than in 14 other DICER1-associated tumors examined (mean 12.9 vs. 6.8 mutations/Mb, p = 0.035). Postoperative care included radiation (n = 5) and chemotherapy (n = 3); at the last follow-up, three patients were alive without DCS, and three had died of disease. Our analysis expands the clinical, histologic, immunohistological, and molecular spectrum of DCS, identifying distinctive features that can aid in the diagnosis, multidisciplinary evaluation, and treatment of DCS.
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http://dx.doi.org/10.1038/s41379-020-0516-1DOI Listing
October 2020

Genomic and Immunologic Characterization of INI1-Deficient Pediatric Cancers.

Clin Cancer Res 2020 06 2;26(12):2882-2890. Epub 2020 Mar 2.

Department of Pediatric Hematology/Oncology, Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts.

Purpose: Several aggressive pediatric cancers harbor alterations in , including rhabdoid tumors, epithelioid sarcoma, and chordoma. As tumor profiling has become more routine in clinical care, we investigated the relationship between genetic variants identified by next-generation sequencing (NGS) and INI1 protein expression. Therapeutic approaches for INI1-deficient tumors are limited. Early reports suggest a potential role for immune checkpoint inhibition in these patients. Thus, we also investigated PD-L1 and CD8 expression in INI1-negative pediatric brain and solid tumors.

Experimental Design: We performed immunohistochemistry (IHC) for INI1 and immune markers (PD-L1, CD8, and CD163) and NGS on tumor samples from 43 pediatric patients who had tumors with INI1 loss on previous IHC or genomic alterations on prior somatic sequencing.

Results: two-copy deletions and inactivating mutations on NGS were associated with loss of INI1 protein expression. Single-copy deletion of was not predictive of INI1 loss in tumor histologies not known to be INI1-deficient. In the 27 cases with INI1 loss and successful tumor sequencing, 24 (89%) had a alteration detected. In addition, 47% (14/30) of the patients with INI1-negative tumors had a tumor specimen that was PD-L1 positive and 60% (18/30) had positive or rare CD8 staining. We report on 3 patients with INI1-negative tumors with evidence of disease control on immune checkpoint inhibitors.

Conclusions: A significant proportion of the INI1-negative tumors express PD-L1, and PD-L1 positivity was associated with extracranial tumor site. These results suggest that clinical trials of immune checkpoint inhibitors are warranted in INI1-negative pediatric cancers.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3089DOI Listing
June 2020

Porous crystals as scaffolds for structural biology.

Curr Opin Struct Biol 2020 02 30;60:85-92. Epub 2019 Dec 30.

Departments of Chemical and Biological Engineering, Biochemistry and Molecular Biology, Chemistry Schools of Biomedical Engineering, Advanced Materials Discovery, Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA. Electronic address:

Molecular scaffolds provide routes to otherwise inaccessible organized states of matter. Scaffolds that are crystalline can be observed in atomic detail using diffraction, along with any guest molecules that have adopted coherent structures therein. This approach, scaffold-assisted structure determination, is not yet routine. However, with varying degrees of guest immobilization, porous crystal scaffolds have recently been decorated with guest molecules. Herein we analyze recent milestones, compare the relative advantages and challenges of different types of scaffold crystals, and weigh the merits of diverse guest installation strategies.
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http://dx.doi.org/10.1016/j.sbi.2019.12.008DOI Listing
February 2020

Renal medullary carcinomas depend upon loss and are sensitive to proteasome inhibition.

Elife 2019 03 12;8. Epub 2019 Mar 12.

Broad Institute of Harvard and MIT, Cambridge, United States.

Renal medullary carcinoma (RMC) is a rare and deadly kidney cancer in patients of African descent with sickle cell trait. We have developed faithful patient-derived RMC models and using whole-genome sequencing, we identified loss-of-function intronic fusion events in one allele with concurrent loss of the other allele. Biochemical and functional characterization of these models revealed that RMC requires the loss of for survival. Through integration of RNAi and CRISPR-Cas9 loss-of-function genetic screens and a small-molecule screen, we found that the ubiquitin-proteasome system (UPS) was essential in RMC. Inhibition of the UPS caused a G2/M arrest due to constitutive accumulation of cyclin B1. These observations extend across cancers that harbor loss, which also require expression of the E2 ubiquitin-conjugating enzyme, . Our studies identify a synthetic lethal relationship between -deficient cancers and reliance on the UPS which provides the foundation for a mechanism-informed clinical trial with proteasome inhibitors.
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http://dx.doi.org/10.7554/eLife.44161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436895PMC
March 2019

Seasonal malaria chemoprevention packaged with malnutrition prevention in northern Nigeria: A pragmatic trial (SMAMP study) with nested case-control.

PLoS One 2019 25;14(1):e0210692. Epub 2019 Jan 25.

Clinton Health Access Initiative, Boston, Massachussetts, United States of America.

Integrating seasonal malaria chemoprevention (SMC), recommended by the WHO since 2012 to prevent malaria infection, with nutrition interventions may improve health outcomes and operational efficiencies. This study assessed the effects of co-packaging interventions on distribution coverage, nutrition, and clinical malaria outcomes in northern Nigeria. From August to November 2014, community volunteers delivered sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) door-to-door each month to approximately 7,000 children aged 6-24 months in seven wards of Madobi, Kano State, Nigeria. In three of the wards children additionally received a lipid-based nutrient supplement (LNS-medium quantity), Plumpy Doz. Coverage, adherence, and anthropometric outcomes were assessed through baseline, midline, and endline household surveys. A facility-based case-control study was also conducted to estimate impact on clinical malaria outcomes. Coverage of SP-AQ was similar between arms at 89% (n = 2,409 child-months [88-90%]) in the SP-AQ only arm and 90% (n = 1,947 child-months [88-92%]) in the SP-AQ plus LNS arm (p = 0.52). Coverage of LNS was 83% (n = 2,409 child-months [81-84%]). Whilst there were marked changes in anthropometric status between baseline, midline and endline, these were largely accounted for by socioeconomic status and must be interpreted with care due to possible measurement issues, especially length-based indices. Overall nutritional status of our most robust measure, weight-for-age, does appear to have improved by endline, but was similar in the two study arms, suggesting no additional benefit of the LNS. While the odds of clinical malaria among those who received the intended intervention were lower in each study arm compared to children who did not receive interventions (SP-AQ only OR = 0.23 [0.09-0.6]; SP-AQ plus LNS OR = 0.22 [0.09-0.55]), LNS was not shown to have an additional impact. Coverage of SMC was high regardless of integrating LNS delivery into the SMC campaign. Supplementation with LNS did not appear to impact nutritional outcomes, but appeared to enhance the impact of SP-AQ on clinical odds of malaria. These results indicate that combining nutritional interventions with seasonal malaria chemoprevention in high-risk areas can be done successfully, warranting further exploration with other products or dosing. Trial Registration: ISRCTN 11413895.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210692PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347255PMC
October 2019

Adapting the Breast Cancer Surgery Decision Quality Instrument for Lower Socioeconomic Status: Improving Readability, Acceptability, and Relevance.

MDM Policy Pract 2018 Jul-Dec;3(2):2381468318811839. Epub 2018 Nov 25.

The Dartmouth Institute for Health Policy & Clinical Practice, Dartmouth College, Lebanon, New Hampshire.

Breast cancer is the second most common malignancy in women. The Decision Quality Instrument (DQI) measures the extent to which patients are informed and involved in breast surgery decisions and receive treatment that aligns with their preferences. There are limited data on the performance of the DQI in women of lower socioeconomic status (SES). Our aims were to 1) examine (and if necessary adapt) the readability, usability, and acceptability of the DQI and 2) explore whether it captures factors important to breast cancer surgery decisions among women of lower SES (relevance). We conducted semistructured cognitive interviews with women of lower SES (based on insurance status, income, and education) who had completed early-stage breast cancer treatments at three cancer centers. We used a two-step thematic analysis with dual independent coding. The study team (including Patient Partners and a Community Advisory Board) reviewed and refined suggested changes. The revised DQI was presented in two focus groups of breast cancer survivors. We conducted 39 interviews. Participants found most parts of the DQI to be helpful and easy to understand. We made the following suggested changes: 1) added a glossary of key terms, 2) added two answer choices and an open text question in the goals and concerns subscale, 3) reworded the treatment intention question, and 4) revised the knowledge subscale instructions since several women disliked the wording and were unsure of what was expected. The readability, usability, acceptability, and relevance of a measure that was primarily developed and validated in women of higher SES required adaptation for optimal use by women of lower SES. Further research will test these adaptations in lower SES populations.
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http://dx.doi.org/10.1177/2381468318811839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262751PMC
November 2018

Detection of Somatic Structural Variants Enables Quantification and Characterization of Circulating Tumor DNA in Children With Solid Tumors.

JCO Precis Oncol 2018 5;2018. Epub 2018 Jul 5.

Dana-Farber Cancer Institute, Boston.

Objective: Liquid biopsies are being rapidly used in adult cancers as new biomarkers of disease. Circulating tumor DNA (ctDNA) levels have been reported to be proportional to disease burden, correlate with treatment response, and predict relapse. However, little is known about how frequently ctDNA is detectable in pediatric patients with solid tumors. Therefore, we developed a next-generation sequencing approach to detect and quantify ctDNA in the blood of patients with the most common pediatric solid tumors.

Methods: Detection of ctDNA requires assays sensitive to somatic events typically observed in the cancer type being studied. In pediatric solid tumors, structural variants are more common than recurrent point mutations. We adapted an ultralow passage whole-genome sequencing approach to capture copy number variants and a hybrid capture sequencing assay to detect translocations in liquid biopsy samples from pediatric patients.

Results: Copy number changes seen by ultralow passage whole-genome sequencing enabled detection of ctDNA in patients with osteosarcoma, neuroblastoma, alveolar rhabdomyosarcoma, and Wilms tumor. In Ewing sarcoma, detection of the translocation was a more sensitive approach. For patients with samples collected at multiple time points, changes in ctDNA levels corresponded to treatment response. We also found that disease-specific genomic biomarkers of prognosis were detectable in ctDNA.

Conclusion: This study demonstrates that liquid biopsy approaches that detect somatic structural variants are well suited to pediatric solid tumors. We show that children with the most common solid tumor malignancies have detectable levels of ctDNA, which may be used to track disease response and identify genomic subclassifiers of disease. Efforts to profile larger collections of clinically annotated specimens are under way to validate the clinical use of these assays.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049092PMC
http://dx.doi.org/10.1200/PO.17.00285DOI Listing
July 2018

Blood collection in cell-stabilizing tubes does not impact germline DNA quality for pediatric patients.

PLoS One 2017 5;12(12):e0188835. Epub 2017 Dec 5.

Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, United States of America.

Objectives: Liquid biopsy technologies allow non-invasive tumor profiling for patients with solid tumor malignancies by sequencing circulating tumor DNA. These studies may be useful in risk-stratification, monitoring for relapse, and understanding tumor evolution. The quality of DNA obtained for these studies is improved when blood samples are collected in tubes that stabilizing white blood cells (WBC). However, ongoing germline research in pediatric oncology generally requires obtaining blood samples in EDTA tubes, which do not contain a WBC-stabilizing preservative. In this study, we explored whether blood samples collected in WBC-stabilizing tubes could be used for both liquid biopsy and germline studies simultaneously, minimizing blood collection volumes for pediatric patients.

Methods: Blood was simultaneously collected from three patients in both EDTA and Streck Cell-Free DNA BCT® tubes. Germline DNA was extracted from all blood samples and subjected to whole-exome sequencing and microarray profiling.

Results: Quality control metrics of DNA quality, sequencing library preperation and whole-exome sequencing alignment were virtually identical regardless of the sample collection method. There was no discernable difference in patterns of variant calling for paired samples by either whole-exome sequencing or microarray analysis.

Conclusion: Our study demonstrates that high-quality genomic studies may be performed from germline DNA obtained in Streck tubes. Therefore, these tubes may be used to simultaneously obtain samples for both liquid biopsy and germline studies in pediatric patients when the volume of blood available for research studies may be limited.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0188835PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716571PMC
December 2017

BET 2: Sharing decisions for patients with suspected cardiac chest pain in the emergency department.

Emerg Med J 2017 Dec;34(12):854-857

Department of Emergency, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

A short-cut review was carried out to establish whether shared decision making used alongside a decision aid can lead to greater patient satisfaction, lower healthcare resource use and non-inferior clinical outcomes in patients with suspected acute coronary syndromes. Four studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that the use of shared decision-making tools in the ED for management of patients with low-risk chest pain appears to be beneficial to the patient and the physician. Use of these shared decision-making tools appears to increase patient knowledge and satisfaction, while decreasing decision conflict and resource use, without causing additional negative outcomes for the patient.
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http://dx.doi.org/10.1136/emermed-2017-207286.2DOI Listing
December 2017

Introducing malaria rapid diagnostic tests in private medicine retail outlets: A systematic literature review.

PLoS One 2017 2;12(3):e0173093. Epub 2017 Mar 2.

Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Background: Many patients with malaria-like symptoms seek treatment in private medicine retail outlets (PMR) that distribute malaria medicines but do not traditionally provide diagnostic services, potentially leading to overtreatment with antimalarial drugs. To achieve universal access to prompt parasite-based diagnosis, many malaria-endemic countries are considering scaling up malaria rapid diagnostic tests (RDTs) in these outlets, an intervention that may require legislative changes and major investments in supporting programs and infrastructures. This review identifies studies that introduced malaria RDTs in PMRs and examines study outcomes and success factors to inform scale up decisions.

Methods: Published and unpublished studies that introduced malaria RDTs in PMRs were systematically identified and reviewed. Literature published before November 2016 was searched in six electronic databases, and unpublished studies were identified through personal contacts and stakeholder meetings. Outcomes were extracted from publications or provided by principal investigators.

Results: Six published and six unpublished studies were found. Most studies took place in sub-Saharan Africa and were small-scale pilots of RDT introduction in drug shops or pharmacies. None of the studies assessed large-scale implementation in PMRs. RDT uptake varied widely from 8%-100%. Provision of artemisinin-based combination therapy (ACT) for patients testing positive ranged from 30%-99%, and was more than 85% in five studies. Of those testing negative, provision of antimalarials varied from 2%-83% and was less than 20% in eight studies. Longer provider training, lower RDT retail prices and frequent supervision appeared to have a positive effect on RDT uptake and provider adherence to test results. Performance of RDTs by PMR vendors was generally good, but disposal of medical waste and referral of patients to public facilities were common challenges.

Conclusions: Expanding services of PMRs to include malaria diagnostic services may hold great promise to improve malaria case management and curb overtreatment with antimalarials. However, doing so will require careful planning, investment and additional research to develop and sustain effective training, supervision, waste-management, referral and surveillance programs beyond the public sector.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173093PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5333947PMC
September 2017

Expanding access to parasite-based malaria diagnosis through retail drug shops in Tanzania: evidence from a randomized trial and implications for treatment.

Malar J 2017 01 3;16(1). Epub 2017 Jan 3.

Tanzania National Malaria Control Programme, Dar es Salaam, Tanzania.

Background: Tanzania has seen a reduction in the fraction of fevers caused by malaria, likely due in part to scale-up of control measures. While national guidelines require parasite-based diagnosis prior to treatment, it is estimated that more than half of suspected malaria treatment-seeking in Tanzania initiates in the private retail sector, where diagnosis by malaria rapid diagnostic test (RDT) or microscopy is illegal. This pilot study investigated whether the introduction of RDTs into Accredited Drug Dispensing Outlets (ADDOs) under realistic market conditions would improve case management practices.

Methods: Dispensers from ADDOs in two intervention districts in Tanzania were trained to stock and perform RDTs and monitored quarterly. Each district was assigned a different recommended retail price to evaluate the need for a subsidy. Malaria RDT and artemisinin-based combination therapy (ACT) uptake and availability were measured pre-intervention and 1 year post-intervention through structured surveys of ADDO owners and exiting customers in both intervention districts and one contiguous control district. Descriptive analysis and logistic regression were used to compare the three districts and identify predictive variables for testing.

Results And Discussion: A total of 310 dispensers from 262 ADDOs were trained to stock and perform RDTs. RDT availability in intervention ADDOs increased from 1% (n = 172) to 73% (n = 163) during the study; ACT medicines were available in 75% of 260 pre-intervention and 68% of 254 post-intervention ADDOs. Pre-treatment testing performed within the ADDO increased from 0 to 65% of suspected malaria patients who visited a shop (95% CI 60.8-69.6%) with no difference between intervention districts. Overall parasite-based diagnosis increased from 19 to 74% in intervention districts and from 3 to 18% in the control district. Prior knowledge of RDT availability (aOR = 1.9, p = 0.03) and RDT experience (aOR = 1.9, p = 0.01) were predictors for testing. Adherence data indicated that 75% of malaria positives received ACT, while 3% of negatives received ACT.

Conclusions: Trained and supervised ADDO dispensers in rural Tanzania performed and sold RDTs under real market conditions to two-thirds of suspected malaria patients during this one-year pilot. These results support the hypothesis that introducing RDTs into regulated private retail sector settings can improve malaria testing and treatment practices without an RDT subsidy. Trial registration ISRCTN ISRCTN14115509.
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http://dx.doi.org/10.1186/s12936-016-1658-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209819PMC
January 2017

The association of area-level social class and tobacco use with adverse breast cancer characteristics among white and black women: evidence from Maryland, 1992-2003.

Int J Health Geogr 2015 Apr 1;14:13. Epub 2015 Apr 1.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Background: In breast cancer, worse disease characteristics are associated with fewer social resources and black race. However, it is unknown whether social gradients have similar impact across race, and whether behaviors, including tobacco use, may explain a portion of the social gradient.

Methods: We modeled relationships between area-level social class, tobacco spending and tumor characteristics, using 50,062 white and black cases diagnosed from 1992-2003 in Maryland, a racially and economically diverse state on the east coast of the United States. Multi-level models estimated the effect of area-level social class and tobacco consumption on tumor grade, size, and stage at diagnosis.

Results: Adjusting for race, age and year of diagnosis, higher social class was associated with lower risk for tumors with histological grade 3 or 4 (O.R. 0.96, 95% C.I. 0.94,0.99), those diagnosed at SEER stage 2 or later (O.R. 0.89, 95% C.I. 0.86, 0.91), and tumor size >2 cm (O.R. 0.87, 95% C.I. 0.84, 0.90). Higher tobacco spending was associated with higher risk for higher grade (O.R. 1.01, 1.00, 1.03) and larger tumors (O.R. 1.03, 95% C.I. 1.01, 1.06), but was not statistically significantly related to later stage (O.R. 1.00, 95% C.I. 0.98, 1.02). Social class was less protective for black women, but tobacco effects were not race-specific.

Conclusions: Results suggest that in one U.S. geographic area, there is a differential protection from social class for black and white women, supporting use of intersectionality theory in breast cancer disparities investigations. Area-level tobacco consumption may capture cases' direct use and second hand smoke exposure, but also may identify neighborhoods with excess cancer-related behavioral or environmental exposures, beyond those measured by social class. Given the growing global burden of both tobacco addiction and aggressive breast cancer, similar investigations across diverse geographic areas are warranted.
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http://dx.doi.org/10.1186/s12942-015-0007-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413983PMC
April 2015

Early complications following cemented modular hip hemiarthroplasty.

Open Orthop J 2015 31;9:15-9. Epub 2015 Jan 31.

Department of Trauma and Orthopaedics, Southmead Hospital, North Bristol NHS Trust, Southmead Way, Bristol, BS10 5NB, UK.

Introduction: Hemiarthroplasty is the recommended treatment for displaced, intracapsular, femoral neck fractures. This study aimed to evaluate the early complications following insertion of the JRI Furlong cemented hemiarthroplasty, a contemporary, modular, double tapered, polished prosthesis.

Method: A series of 459 consecutive patients (May 2006 - June 2009) treated with a JRI hemiarthroplasty with a minimum of one-year (1-4years) follow-up were evaluated. Data collected retrospectively from clinical records and hospital databases included patient demographics, mortality, deep infection, dislocation, periprosthetic fracture, and any requirement for revision or complications related to the prosthesis.

Results: Full data were available for 429 of 459 (93%), partial data for 30 (7%). Average age was 83 years (52-100), 76% were female. One-year mortality was 24%. Intraoperative fractures occurred in 17 patients (3.7%). There were two intraoperative deaths. There were nine early deep wound infections (2%). There were two revisions to total hip replacement (THR), four patients required conversion to THR and one underwent an excision arthroplasty procedure.

Discussion: Early surgical outcomes for the JRI hemiarthroplasty prosthesis are equivalent or superior to other major hemiarthroplasty prostheses previously reported however, there was a high intraoperative fracture rate of 3.7%. We recommend using a stem one size smaller than the final broach in fragile, osteoporotic bone. No patients re-presented with aseptic loosening or stem failure.
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http://dx.doi.org/10.2174/1874325001509010015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323769PMC
February 2015

Strengthening malaria diagnosis and appropriate treatment in Namibia: a test of case management training interventions in Kavango Region.

Malar J 2014 Dec 18;13:508. Epub 2014 Dec 18.

Clinton Health Access Initiative, Boston, MA 02127, USA.

Background: Despite its importance in control and elimination settings, malaria diagnosis rates tend to be low in many African countries. An operational research pilot was conducted in Namibia to identify the key barriers to appropriate diagnosis of malaria in public health facilities and to evaluate the effectiveness of various training approaches in improving the uptake and adherence to rapid diagnostic tests (RDTs).

Methods: After identifying case management weaknesses through focus group discussions, training interventions were designed to address these barriers over a six-month period. The study had three intervention districts and one control within the Kavango region of Namibia where poor case management practices were observed. The interventions included an enhanced training model, clinical mentorship, and SMS reminders. Monthly data on testing and treatment were collected for the period of April to September 2012 and, for comparison, the same months during the prior year from all 52 health facilities in Kavango. The same indicators were also obtained at district level for a follow-up period of 15 months from October 2012 to December 2013 to observe whether any improvements were sustained over time.

Results: All intervention arms produced significant improvements in case management practices compared to the control district (all p < 0.02). Overall, districts receiving any training improved testing rates from 25% to 66% at minimum compared to the control. The enhanced training plus mentorship arm resulted in a significantly greater proportion of fevers receiving RDTs compared to the district receiving enhanced training alone, increasing from 27% to over 90% at endline. No ACT was prescribed to untested patients after caregivers received mentorship or SMS reminders. These improvements were all sustained over the 15-month follow-up.

Conclusions: These changes show a reversal of improper case management practices over the six-month study period and demonstrate that implementing simple training interventions can have a significant, sustainable impact on the uptake of and adherence to malaria RDTs. Findings from this work have already informed Namibia's roll out of a more robust case management training programme. The approaches used in Namibia may be applicable to other resource-constrained countries, providing practical guidance on sustainable approaches to febrile illness management.
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http://dx.doi.org/10.1186/1475-2875-13-508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301656PMC
December 2014

Price subsidies increase the use of private sector ACTs: evidence from a systematic review.

Health Policy Plan 2015 Apr 14;30(3):397-405. Epub 2014 Mar 14.

Clinton Health Access Initiative, 383 Dorchester Avenue, Suite 400, Boston, MA, USA and Slingshot, 67 Riverside Dr. Nairobi Kenya 00100 London, UK.

Background: Although artemisinin combination therapies (ACTs) are the recommended first-line treatment for uncomplicated malaria in most endemic countries, they have been prohibitively expensive in the retail sector where many suspected malaria cases purchase treatment. ACT subsidies seek to stimulate consumer demand for the drugs over cheaper but often ineffective alternatives by reducing their prices. Recent evidence from eight regions implementing such subsidies suggests that they are generally successful in improving availability of the drugs and decreasing their retail prices, but it remains unclear whether these outcomes translate to improved use by patients with suspected malaria.

Methods: A systematic literature review was conducted to identify reports of experimental or programmatic ACT subsidies to assess the impact of subsidies on consumer use. Relationships between price, use and potential confounding factors were examined using logistic and repeated measures binomial regression models, and approximate magnitudes of associations were assessed with linear regression. In total, 40 studies, 14 peer-reviewed and 26 non-peer-reviewed, were eligible for inclusion in the analysis. The reviewed studies found a substantial increase in private sector ACT use following the introduction of a subsidy. Overall, each $1 decrease in price was linked to a 24 percentage point increase in the fraction of suspected malaria cases purchasing ACTs (R(2) = 0.302). No significant differences were evident in this relationship when comparing the poorest and richest groups, rural vs urban populations or children vs adults.

Conclusions: These findings suggest that ACT price reductions can increase their use for suspected malaria, even within poorer, more remote populations that may be most at risk of malaria mortality. Whether a subsidy is appropriate will depend upon local context, including treatment-seeking behaviours and malaria prevalence. This review provides an initial foundation for policymakers to make evidence-based decisions regarding ACT price reductions to increase use of potentially life-saving drugs.
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http://dx.doi.org/10.1093/heapol/czu013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4353896PMC
April 2015

Improving handover of patient care using a new weekend proforma with a focus on ceiling of care.

BMJ Qual Improv Rep 2014 1;3(1). Epub 2014 Oct 1.

North Bristol NHS Trust.

Patient handover is paramount for effective patient care and is often poorly documented or incomplete. North Bristol NHS Trust weekend handover proformas identify medical patients requiring weekend review. Many patients seen during on-call shifts are not handed over. Our aim was to develop Friday ward round proforma sheets for medical patients, to encourage clear documentation of management plans in order to improve handover of important information, particularly ceiling of care decisions. Questionnaires were completed by F1 doctors regarding current handover systems. Baseline data collected by on-call F1s included time of understanding a patient's ceiling of care decision, and difficulty of comprehension of medical notes. Repeat data were collected with novel proformas in situ. Multiple cycles were performed to refine the sheets and target problems arising in their use. Ninety-three percent of F1s wanted improved patient handover, with ceiling of care (87%) and management plans (73%) being the most difficult areas to understand. Time taken to ascertain ceiling of care decisions improved with the introduction of Friday handover proformas; mean time 153 seconds before and 5 seconds after. Clarity and documentation of management plans improved, with 50% improvement in ease of understanding medical notes. Results demonstrate that introducing Friday ward round proformas for medical patients improves communication between weekday and on-call teams, highlights current escalation of care plans, and leads to faster decision-making. Future plans include the introduction of a short educational session to the new F1 doctors and continued progress with introduction into hospital stationary.
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http://dx.doi.org/10.1136/bmjquality.u203623.w1804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949620PMC
August 2016

Malaria resurgence: a systematic review and assessment of its causes.

Malar J 2012 Apr 24;11:122. Epub 2012 Apr 24.

Clinton Health Access Initiative, Boston, MA, USA.

Background: Considerable declines in malaria have accompanied increased funding for control since the year 2000, but historical failures to maintain gains against the disease underscore the fragility of these successes. Although malaria transmission can be suppressed by effective control measures, in the absence of active intervention malaria will return to an intrinsic equilibrium determined by factors related to ecology, efficiency of mosquito vectors, and socioeconomic characteristics. Understanding where and why resurgence has occurred historically can help current and future malaria control programmes avoid the mistakes of the past.

Methods: A systematic review of the literature was conducted to identify historical malaria resurgence events. All suggested causes of these events were categorized according to whether they were related to weakened malaria control programmes, increased potential for malaria transmission, or technical obstacles like resistance.

Results: The review identified 75 resurgence events in 61 countries, occurring from the 1930s through the 2000s. Almost all resurgence events (68/75 = 91%) were attributed at least in part to the weakening of malaria control programmes for a variety of reasons, of which resource constraints were the most common (39/68 = 57%). Over half of the events (44/75 = 59%) were attributed in part to increases in the intrinsic potential for malaria transmission, while only 24/75 (32%) were attributed to vector or drug resistance.

Conclusions: Given that most malaria resurgences have been linked to weakening of control programmes, there is an urgent need to develop practical solutions to the financial and operational threats to effectively sustaining today's successful malaria control programmes.
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http://dx.doi.org/10.1186/1475-2875-11-122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458906PMC
April 2012
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