A Framework for the Development of Living Practice Guidelines in Health Care.

BACKGROUND: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. OBJECTIVE: To develop a framework that characterizes the processes of development of living practice guidelines in health care. DESIGN: First, 3 background reviews were conducted: a scoping review of methods papers, a review of handbooks of guideline-producing organizations, and an analytic review of selected living practice guidelines. Second, the core team drafted the first version of the framework. Finally, the core team refined the framework through an online survey and online discussions with a multidisciplinary international group of stakeholders. SETTING: International. PARTICIPANTS: Multidisciplinary group of 51 persons who have experience with guidelines. MEASUREMENTS: Not applicable. RESULTS: A major principle of the framework is that the unit of update in a living guideline is the individual recommendation. In addition to providing definitions, the framework addresses several processes. The planning process should address the organization's adoption of the living methodology as well as each specific guideline project. The production process consists of initiation, maintenance, and retirement phases. The reporting should cover the evidence surveillance time stamp, the outcome of reassessment of the body of evidence (when applicable), and the outcome of revisiting a recommendation (when applicable). The dissemination process may necessitate the use of different venues, including one for formal publication. LIMITATION: This study does not provide detailed or practical guidance for how the described concepts would be best implemented. CONCLUSION: The framework will help guideline developers in planning, producing, reporting, and disseminating living guideline projects. It will also help research methodologists study the processes of living guidelines. PRIMARY FUNDING SOURCE: None.

Measuring health inequalities in the context of sustainable development goals.

Transforming our world: the 2030 agenda for sustainable development promotes the improvement of health equity, which entails ongoing monitoring of health inequalities. The World Health Organization has developed a multistep approach to health inequality monitoring consisting of: (i) determining the scope of monitoring; (ii) obtaining data; (iii) analysing data; (iv) reporting results; and (v) implementing changes. Technical considerations at each step have implications for the results and conclusions of monitoring and subsequent remedial actions. This paper presents some technical considerations for developing or strengthening health inequality monitoring, with the aim of encouraging more robust, systematic and transparent practices. We discuss key aspects of measuring health inequalities that are relevant to steps (i) and (iii). We highlight considerations related to the selection, measurement and categorization of dimensions of health inequality, as well as disaggregation of health data and calculation of summary measures of inequality. Inequality monitoring is linked to health and non-health aspects of the 2030 agenda for sustainable development, and strong health inequality monitoring practices can help to inform equity-oriented policy directives.

Transformer notre monde: le programme de développement durable à l'horizon 2030 promeut l'amélioration de l'équité en santé, ce qui implique un suivi continu des inégalités en matière de santé. L'Organisation mondiale de la Santé a élaboré une approche pour le suivi des inégalités en santé qui comprend plusieurs étapes: (i) déterminer la portée du suivi; (ii) collecter des données; (iii) analyser les données; (iv) communiquer les résultats; et (v) mettre en œuvre des changements. À chaque étape, des considérations techniques ont des conséquences sur les résultats et les conclusions du suivi et sur les mesures correctives qui en résultent. Ce document présente certaines considérations techniques pour le développement ou le renforcement du suivi des inégalités en santé, dans l'objectif d'encourager des pratiques plus fiables, plus systématiques et plus transparentes. Nous examinons des aspects clés de la mesure des inégalités en santé à prendre en compte dans les étapes (i) et (iii). Nous mettons en avant des considérations en lien avec la sélection, la mesure et la catégorisation des dimensions des inégalités en matière de santé, ainsi que la ventilation des données sur la santé et le calcul de mesures synthétiques des inégalités. Le suivi des inégalités est lié à des aspects sanitaires et non sanitaires du Programme de développement durable à l'horizon 2030, et des pratiques rigoureuses de suivi des inégalités en matière de santé peuvent contribuer à éclairer les directives axées sur l'équité.

Transformar nuestro mundo: el plan de 2030 para el desarrollo sostenible promueve la mejora de la igualdad en la salud, lo que implica un seguimiento continuo de las desigualdades en salud. La Organización Mundial de la Salud ha desarrollado un enfoque de múltiples pasos para el seguimiento de la desigualdad en la salud que consiste en: (i) determinar el alcance del seguimiento; (ii) obtener datos; (iii) analizar los datos; (iv) informar sobre los resultados; e (v) implementar los cambios. Las consideraciones técnicas de cada paso tienen implicaciones para los resultados y las conclusiones del seguimiento y las acciones correctivas subsiguientes. En este documento se presentan algunas consideraciones técnicas para desarrollar o fortalecer el seguimiento de la desigualdad en la salud, con el fin de fomentar prácticas más robustas, sistemáticas y transparentes. Se analizan aspectos clave de la medición de las desigualdades en la salud relevantes para los pasos (i) y (iii). Se destacan las consideraciones relacionadas con la selección, la medición y la categorización de las dimensiones de la desigualdad en la salud, así como la desagregación de los datos de salud y el cálculo de medidas sintetizadas de desigualdad. El seguimiento de la desigualdad está vinculado a los aspectos sanitarios y no sanitarios del programa de desarrollo sostenible de 2030, y unas prácticas rigurosas de seguimiento de la desigualdad en la salud pueden ayudar a fundamentar las directrices políticas orientadas a la igualdad.

Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement.

Measurements of health indicators are rarely available for every population and period of interest, and available data may not be comparable. The Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) define best reporting practices for studies that calculate health estimates for multiple populations (in time or space) using multiple information sources. Health estimates that fall within the scope of GATHER include all quantitative population-level estimates (including global, regional, national, or subnational estimates) of health indicators, including indicators of health status, incidence and prevalence of diseases, injuries, and disability and functioning; and indicators of health determinants, including health behaviours and health exposures. GATHER comprises a checklist of 18 items that are essential for best reporting practice. A more detailed explanation and elaboration document, describing the interpretation and rationale of each reporting item along with examples of good reporting, is available on the GATHER website.

Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement.

Gretchen Stevens and colleagues present the GATHER statement, which seeks to promote good practice in the reporting of global health estimates.

Correction: Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement.

[This corrects the article DOI: 10.1371/journal.pmed.1002056.].

Deconstructing the differences: a comparison of GBD 2010 and CHERG's approach to estimating the mortality burden of diarrhea, pneumonia, and their etiologies.

BACKGROUND: Pneumonia and diarrhea are leading causes of death for children under five (U5). It is challenging to estimate the total number of deaths and cause-specific mortality fractions. Two major efforts, one led by the Institute for Health Metrics and Evaluation (IHME) and the other led by the World Health Organization (WHO)/Child Health Epidemiology Reference Group (CHERG) created estimates for the burden of disease due to these two syndromes, yet their estimates differed greatly for 2010. METHODS: This paper discusses three main drivers of the differences: data sources, data processing, and covariates used for modelling. The paper discusses differences in the model assumptions for etiology-specific estimates and presents recommendations for improving future models. RESULTS: IHME's Global Burden of Disease (GBD) 2010 study estimated 6.8 million U5 deaths compared to 7.6 million U5 deaths from CHERG. The proportional differences between the pneumonia and diarrhea burden estimates from the two groups are much larger; GBD 2010 estimated 0.847 million and CHERG estimated 1.396 million due to pneumonia. Compared to CHERG, GBD 2010 used broader inclusion criteria for verbal autopsy and vital registration data. GBD 2010 and CHERG used different data processing procedures and therefore attributed the causes of neonatal death differently. The major difference in pneumonia etiologies modeling approach was the inclusion of observational study data; GBD 2010 included observational studies. CHERG relied on vaccine efficacy studies. DISCUSSION: Greater transparency in modeling methods and more timely access to data sources are needed. In October 2013, the Bill & Melinda Gates Foundation (BMGF) hosted an expert meeting to examine possible approaches for better estimation. The group recommended examining the impact of data by systematically excluding sources in their models. GBD 2.0 will use a counterfactual approach for estimating mortality from pathogens due to specific etiologies to overcome bias of the methods used in GBD 2010 going forward.

Count every newborn; a measurement improvement roadmap for coverage data.

BACKGROUND: The Every Newborn Action Plan (ENAP), launched in 2014, aims to end preventable newborn deaths and stillbirths, with national targets of ≤12 neonatal deaths per 1000 live births and ≤12 stillbirths per 1000 total births by 2030. This requires ambitious improvement of the data on care at birth and of small and sick newborns, particularly to track coverage, quality and equity. METHODS: In a multistage process, a matrix of 70 indicators were assessed by the Every Newborn steering group. Indicators were graded based on their availability and importance to ENAP, resulting in 10 core and 10 additional indicators. A consultation process was undertaken to assess the status of each ENAP core indicator definition, data availability and measurement feasibility. Coverage indicators for the specific ENAP treatment interventions were assigned task teams and given priority as they were identified as requiring the most technical work. Consultations were held throughout. RESULTS: ENAP published 10 core indicators plus 10 additional indicators. Three core impact indicators (neonatal mortality rate, maternal mortality ratio, stillbirth rate) are well defined, with future efforts needed to focus on improving data quantity and quality. Three core indicators on coverage of care for all mothers and newborns (intrapartum/skilled birth attendance, early postnatal care, essential newborn care) have defined contact points, but gaps exist in measuring content and quality of the interventions. Four core (antenatal corticosteroids, neonatal resuscitation, treatment of serious neonatal infections, kangaroo mother care) and one additional coverage indicator for newborns at risk or with complications (chlorhexidine cord cleansing) lack indicator definitions or data, especially for denominators (population in need). To address these gaps, feasible coverage indicator definitions are presented for validity testing. Measurable process indicators to help monitor health service readiness are also presented. A major measurement gap exists to monitor care of small and sick babies, yet signal functions could be tracked similarly to emergency obstetric care. CONCLUSIONS: The ENAP Measurement Improvement Roadmap (2015-2020) outlines tools to be developed (e.g., improved birth and death registration, audit, and minimum perinatal dataset) and actions to test, validate and institutionalise proposed coverage indicators. The roadmap presents a unique opportunity to strengthen routine health information systems, crosslinking these data with civil registration and vital statistics and population-based surveys. Real measurement change requires intentional transfer of leadership to countries with the greatest disease burden and will be achieved by working with centres of excellence and existing networks.

Cognitive performance related to HIV-1-infected monocytes.

The effect that HIV type 1 (HIV) has on neurocognition is a dynamic process whereby peripheral events are likely involved in setting the stage for clinical findings. In spite of antiretroviral therapy (ART), patients continue to be at risk for HIV-associated neurocognitive disorders (HAND), which might be related to persistence of inflammation. In a yearly assessment of HIV DNA levels in activated monocytes, increased HIV DNA copies were found in patients with persistent HAND. Furthermore, activated monocytes from patients with high HIV DNA copies secreted more inflammatory cytokines. Since these activated monocytes traffic to the CNS and enter the brain, they may contribute to an inflammatory environment in the CNS that leads to HAND.

Methods for evaluating the impact of vertical programs on health systems: protocol for a study on the impact of the global polio eradication initiative on strengthening routine immunization and primary health care.

BACKGROUND: The impact of vertical programs on health systems is a much-debated topic, and more evidence on this complex relationship is needed. This article describes a research protocol developed to assess the relationship between the Global Polio Eradication Initiative, routine immunization, and primary health care in multiple settings. METHODS/DESIGN: This protocol was designed as a combination of quantitative and qualitative research methods, making use of comparative ethnographies. The study evaluates the impact of the Global Polio Eradication Initiative on routine immunization and primary health care by: (a) combining quantitative and qualitative work into one coherent study design; (b) using purposively selected qualitative case studies to systematically evaluate the impact of key contextual variables; and (c) making extensive use of the method of participant observation to create comparative ethnographies of the impact of a single vertical program administered in varied contexts. DISCUSSION: The study design has four major benefits: (1) the careful selection of a range of qualitative case studies allowed for systematic comparison; (2) the use of participant observation yielded important insights on how policy is put into practice; (3) results from our quantitative analysis could be explained by results from qualitative work; and (4) this research protocol can inform the creation of actionable recommendations. Here, recommendations for how to overcome potential challenges in carrying out such research are presented. This study illustrates the utility of mixed-methods research designs in which qualitative data are not just used to embellish quantitative results, but are an integral component of the analysis.

A Rare Case of Granular Cell Tumor in the Right Upper Lung of an Adolescent Patient.

Granular cell tumors (GCTs) are rare neoplasms of neuroectodermal origin characterized by large polygonal cells with abundant eosinophilic and granular cytoplasm. GCTs rarely affect the lungs, with only a few cases reported in the literature. The pathophysiology of this Schwann cell-derived condition is not well understood but is thought to be due to recurring genetic mutations. GCTs have been linked with Noonan syndrome. Here, we report the case of a 17-year-old caucasian male who presented with partial upper airway obstruction due to a GCT. This case promotes awareness among pathologists and clinicians for this condition in the workup of patients presenting with upper airway obstruction.

A Rare Case of Sarcoidosis Involving Male Breast Tissue.

Sarcoidosis is a multisystem, inflammatory granulomatous disease that rarely involves breast tissue. The pathophysiology of this chronic granulomatous condition is not well understood but is thought to be multifactorial, involving environmental influences causing an amplified immune response. A key histomorphology feature in sarcoidosis is the presence of non-necrotizing granulomas. In this case, we report a 41-year-old African-American man with a known history of sarcoidosis of the lung who presented with gynecomastia and bilateral breast tenderness with palpable nodules. Subsequent biopsy and microscopic examination of the breast nodules revealed diffuse involvement with non-necrotizing granulomas in both breasts. A final diagnosis of extensive sarcoidosis involving breast tissue was rendered after excluding other causes of non-necrotizing granulomas. The patient underwent a bilateral mastectomy to remove the breast nodules. This case discusses sarcoidosis involving an unusual site.

A Case Report of the Ongoing Management and Comorbidities of Loin Pain Hematuria Syndrome with an Unusual Presentation.

Loin pain hematuria syndrome (LPHS) is a rare chronic pain disorder that is poorly understood. LPHS presents as unilateral or bilateral flank pain with hematuria of unknown cause. The lack of knowledge surrounding pathogenesis and effective treatment has resulted in missed diagnoses as well as narcotic addiction in some patients. In this case, we describe the presentation and management of a 30-year-old female with a history of anxiety, depression, chronic pelvic bleeding, and pain recently diagnosed with LPHS after a total hysterectomy. She presented with ongoing pelvic pain symptoms with recent tachycardia, recurrent urinary tract infections, and nephrolithiasis. Loin pain hematuria presents as a particularly rare and difficult diagnosis to manage with multiple, sometimes unpredictable, comorbidities. This case serves as an example of a unique presentation with additional uncommon symptoms.

A Collision Tumor in the Breast Consisting of Invasive Ductal Carcinoma and Malignant Melanoma.

Collision tumors are rare neoplasms that consist of at least two different cell lineages at the same site. Given the many possible combinations that can occur, collision tumors, while rare, have been reported in multiple locations such as the stomach, bladder, and thyroid. Collision tumors are rarely found in breast tissue, with only a few cases reported in the literature. We herein report a unique case of a 79-year-old woman with a history of melanoma who presented with a left breast mass that was subsequently found to have invasive ductal carcinoma (IDC) and metastatic melanoma in the breast tissue. This is one of the first reported combinations of these two malignancies.

Short-term storage of human spermatozoa in electrolyte-free medium without freezing maintains sperm chromatin integrity better than cryopreservation.

Previous attempts to maintain human spermatozoa without freezing were based on short-term storage in component-rich medium and led to fast decline in motility and increased incidence of chromosome breaks. Here we report a new method in which sperm are maintained without freezing in an electrolyte-free medium (EFM) composed of glucose and bovine serum albumin. Human sperm were stored in EFM or human tubal fluid medium (HTFM) or were cryopreserved, and their motility, viability, and DNA integrity were examined at different intervals. Cryopreservation led to significant decline in sperm motility and viability and induced DNA fragmentation. Sperm stored in EFM maintained motility and viability for up to 4 and 7 wk, respectively, much longer than sperm stored in HTFM (<2 and <4 wk, respectively). DNA integrity, assessed with comet assay, was also maintained significantly better in EFM than in HTFM. One-week storage in EFM yielded motility and viability similar to that of cryopreserved sperm, but DNA integrity was significantly higher, resembling that of fresh sperm. After several weeks of storage in EFM, sperm were able to activate oocytes, undergo chromatin remodeling, and form normal zygotic chromosomes after intracytoplasmic sperm injection. This study demonstrated that human spermatozoa can be stored in EFM without freezing for several weeks while maintaining motility, viability, and chromatin integrity and that 1-wk storage in EFM offers better protection of sperm DNA integrity than cryopreservation. Sperm storage in EFM may become a viable option for the physicians working in assisted reproduction technology clinics, which would avoid cryodamage.

FOXO3A genotype is strongly associated with human longevity.

Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity. However, to date human data have been scarce. Studies have been hampered by small sample sizes, lack of precise phenotyping, and population stratification, among other challenges. Therefore, to more precisely assess potential genetic contributions to human longevity from genes linked to IIS signaling, we chose a large, homogeneous, long-lived population of men well-characterized for aging phenotypes, and we performed a nested-case control study of 5 candidate longevity genes. Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs. homozygous major alleles between the cases and controls was 2.75 (P = 0.00009; adjusted P = 0.00135). Long-lived men also presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls. Several of these aging phenotypes were associated with FOXO3A genotype. Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity and this was associated with homozygosity for the FOXO3A GG genotype. Further exploration of the FOXO3A gene, human longevity and other aging phenotypes is warranted in other populations.