Aspects Èpidémiologiques et Cliniques des Cervicalgies non Traumatiques en Consultation de Rhumatologie à Bouaké

Objectif : Etudier les caractéristiques épidémiologiques et diagnostiques des cervicalgies non traumatiques (CNT) chez une population noire d’Afrique sub-saharienne. Patients et méthodes : Etude rétrospective descriptive sur une période de six ans, de Janvier 2014 à Décembre 2019 portant sur les patients vus pour une CNT en consultation de rhumatologie à Bouaké en Côte d’ Ivoire. Résultats : Sur 4036 patients vus pour une affection rhumatologique, 130 avaient une CNT soit une fréquence de 3,2%. L’âge moyen des patients était de 54,03 ± 13,71 ans et le sex ratio de 0,8. Le groupe d’âge de 40 à 70 ans représentait 74,6 % des patients (97 cas). Les patients consultaient surtout pour une forte douleur à début progressif (56,2%), d’évolution chronique (63,9%), et une monoparésie brachiale était observée dans quatre cas (3,1%). Il s’agissait surtout d’une cervicalgie isolée (63,1%), parfois associée à une névralgie cervico-brachiale (9,2%), à une rachialgie dorsolombaire (18,5%) ou à une arthralgie périphérique (9,2%). La radiographie standard (94,6%) était l’imagerie la plus prescrite. Les diagnostics retenus étaient la cervicalgie commune (87,7%), la polyarthrite rhumatoïde (4,6%), le mal de Pott (3,1%), une métastase de cancer de la prostate (1,5%), et le myélome multiple (3,1%). Soixante-douze patients (55,4%) avaient entrepris une automédication avant la consultation avec des anti-inflammatoires dans 43,1% des cas et des antibiotiques dans 4,2%. Conclusion : La CNT n’est pas rare en consultation rhumatologique à Bouaké. Elle touche surtout les patients entre 40 et 70 ans et les femmes sont les plus concernées. La cervicalgie commune est le diagnostic le plus fréquent.   Objective: To study the epidemiological and diagnostic features of non-traumatic neck pain in a black sub-Saharan African population. Patients and methods: Retrospective descriptive study over a six-year period, from January 2014 to December 2019 covering patients seen for non-traumatic neck pain in rheumatology consultation in Bouaké, Côte d' Ivoire. Results: Of 4036 patients seen for a rheumatological condition, 130 had non-traumatic neck pain, a frequency of 3.2%. The mean age of patients was 54.03 ± 13.71 years, and the sex ratio was 0.8.  The 40-70 age group accounted for 74.6% of patients (97 cases). Patients mainly consulted for severe pain with progressive onset (56.2%), chronic evolution (63.9%), and brachial monoparesis was observed in four cases (3.1%). The pain was mainly isolated cervicalgia (63.1%), sometimes associated with cervicobrachial neuralgia (9.2%), dorsolumbar spinalgia (18.5%) or peripheral arthralgia (9.2%). Standard radiography (94.6%) was the most frequently prescribed imaging technique. The most common diagnoses were common neck pain (87.7%), rheumatoid arthritis (4.6%), Pott's disease (3.1%), prostatic metastasis (1.5%), and multiple myeloma (3.1%). Seventy-two patients (55.4%) had undertaken self-medication prior to consultation, with non-steroidal anti-inflammatory drugs in 43.1% of cases and antibiotics in 4.2%. Conclusion: Non-traumatic neck pain is not uncommon in rheumatology consultations in Bouaké. It mainly affects patients between 40 and 70 years of age, and women are most affected. Common cervicalgia is the most frequent diagnosis

Aspects Èpidémiologiques et Cliniques des Cervicalgies non Traumatiques en Consultation de Rhumatologie à Bouaké

Objectif : Etudier les caractéristiques épidémiologiques et diagnostiques des cervicalgies non traumatiques (CNT) chez une population noire d’Afrique sub-saharienne. Patients et méthodes : Etude rétrospective descriptive sur une période de six ans, de Janvier 2014 à Décembre 2019 portant sur les patients vus pour une CNT en consultation de rhumatologie à Bouaké en Côte d’ Ivoire. Résultats : Sur 4036 patients vus pour une affection rhumatologique, 130 avaient une CNT soit une fréquence de 3,2%. L’âge moyen des patients était de 54,03 ± 13,71 ans et le sex ratio de 0,8. Le groupe d’âge de 40 à 70 ans représentait 74,6 % des patients (97 cas). Les patients consultaient surtout pour une forte douleur à début progressif (56,2%), d’évolution chronique (63,9%), et une monoparésie brachiale était observée dans quatre cas (3,1%). Il s’agissait surtout d’une cervicalgie isolée (63,1%), parfois associée à une névralgie cervico-brachiale (9,2%), à une rachialgie dorsolombaire (18,5%) ou à une arthralgie périphérique (9,2%). La radiographie standard (94,6%) était l’imagerie la plus prescrite. Les diagnostics retenus étaient la cervicalgie commune (87,7%), la polyarthrite rhumatoïde (4,6%), le mal de Pott (3,1%), une métastase de cancer de la prostate (1,5%), et le myélome multiple (3,1%). Soixante-douze patients (55,4%) avaient entrepris une automédication avant la consultation avec des anti-inflammatoires dans 43,1% des cas et des antibiotiques dans 4,2%. Conclusion : La CNT n’est pas rare en consultation rhumatologique à Bouaké. Elle touche surtout les patients entre 40 et 70 ans et les femmes sont les plus concernées. La cervicalgie commune est le diagnostic le plus fréquent.   Objective: To study the epidemiological and diagnostic features of non-traumatic neck pain in a black sub-Saharan African population. Patients and methods: Retrospective descriptive study over a six-year period, from January 2014 to December 2019 covering patients seen for non-traumatic neck pain in rheumatology consultation in Bouaké, Côte d' Ivoire. Results: Of 4036 patients seen for a rheumatological condition, 130 had non-traumatic neck pain, a frequency of 3.2%. The mean age of patients was 54.03 ± 13.71 years, and the sex ratio was 0.8.  The 40-70 age group accounted for 74.6% of patients (97 cases). Patients mainly consulted for severe pain with progressive onset (56.2%), chronic evolution (63.9%), and brachial monoparesis was observed in four cases (3.1%). The pain was mainly isolated cervicalgia (63.1%), sometimes associated with cervicobrachial neuralgia (9.2%), dorsolumbar spinalgia (18.5%) or peripheral arthralgia (9.2%). Standard radiography (94.6%) was the most frequently prescribed imaging technique. The most common diagnoses were common neck pain (87.7%), rheumatoid arthritis (4.6%), Pott's disease (3.1%), prostatic metastasis (1.5%), and multiple myeloma (3.1%). Seventy-two patients (55.4%) had undertaken self-medication prior to consultation, with non-steroidal anti-inflammatory drugs in 43.1% of cases and antibiotics in 4.2%. Conclusion: Non-traumatic neck pain is not uncommon in rheumatology consultations in Bouaké. It mainly affects patients between 40 and 70 years of age, and women are most affected. Common cervicalgia is the most frequent diagnosis

Interleukin and Growth Factor Levels in Subretinal Fluid in Rhegmatogenous Retinal Detachment: A Case-Control Study

BACKGROUND: Rhegmatogenous retinal detachment (RRD) is a major cause of visual loss in developed countries. Proliferative vitreoretinopathy (PVR), an eye-sight threatening complication of RRD surgery, resembles a wound-healing process with inflammation, scar tissue formation, and membrane contraction. This study was performed to determine the possible involvement of a wide range of cytokines in the future development of PVR, and to identify predictors of PVR and visual outcome. METHODOLOGY: A multiplex immunoassay was used for the simultaneous detection of 29 different cytokines in subretinal fluid samples from patients with primary RRD. Of 306 samples that were collected and stored in our BioBank between 2001 and 2008, 21 samples from patients who developed postoperative PVR were compared with 54 age-, sex-, and storage-time-matched RRD control patients who had an uncomplicated postoperative course during the overall follow-up period. FINDINGS: Levels of IL-1α, IL-2, IL-3, IL-6, VEGF, and ICAM-1 were significantly higher (P<0.05) in patients who developed postoperative PVR after reattachment surgery than in patients with an uncomplicated postoperative course, whereas levels of IL-1β, IL-4, IL-5, IL-7, IL-9, IL-10, IL-11, IL-12p70, IL-13, IL-15, IL-17, IL-18, IL-21, IL-22, IL-23, IL-25, IL-33, TNF-α, IFN-γ, IGF-1, bFGF, HGF, and NGF were not (P>0.05). Multivariate logistic regression analysis revealed that IL-3 (P = 0.001), IL-6 (P = 0.047), ICAM-1 (P = 0.010), and preoperative visual acuity (P = 0.026) were independent predictors of postoperative PVR. Linear regression analysis showed that ICAM-1 (P = 0.005) and preoperative logMAR visual acuity (P = 0.001) were predictive of final visual outcome after primary RRD repair. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that after RRD onset an exaggerated response of certain cytokines may predispose to PVR. Sampling at a time close to the onset of primary RRD may thus provide clues as to which biological events may initiate the development of PVR and, most importantly, may provide a means for therapeutic control

Intestinal Obstruction Syndromes in Cystic Fibrosis: Meconium Ileus, Distal Intestinal Obstruction Syndrome, and Constipation

Meconium ileus at birth, distal intestinal obstruction syndrome (DIOS), and constipation are an interrelated group of intestinal obstruction syndromes with a variable severity of obstruction that occurs in cystic fibrosis patients. Long-term follow-up studies show that today meconium ileus is not a risk factor for impaired nutritional status, pulmonary function, or survival. DIOS and constipation are frequently seen in cystic fibrosis patients, especially later in life; genetic, dietary, and other associations have been explored. Diagnosis of DIOS is based on suggestive symptoms, with a right lower quadrant mass confirmed on abdominal radiography, whereas symptoms of constipation are milder and of longer standing. In DIOS, early aggressive laxative treatment with oral laxatives (polyethylene glycol) or intestinal lavage with balanced osmotic electrolyte solution and rehydration is required, which now makes the need for surgical interventions rare. Constipation can generally be well controlled with polyethylene glycol maintenance treatment

Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells

Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships

The DAC system and associations with acute leukemias and myelodysplastic syndromes

Imbalances of histone acetyltransferase (HAT) and deacetylase activity (DAC) that result in deregulated gene expression are commonly observed in leukemias. These alterations provide the basis for novel therapeutic approaches that target the epigenetic mechanisms implicated in leukemogenesis. As the acetylation status of histones has been linked to transcriptional regulation of genes involved particularly in differentiation and apoptosis, DAC inhibitors (DACi) have attracted considerable attention for treatment of hematologic malignancies. DACi encompass a structurally diverse family of compounds that are being explored as single agents as well as in combination with chemotherapeutic drugs, small molecule inhibitors of signaling pathways and hypomethylating agents. While DACi have shown clear evidence of activity in acute myeloid leukemia, myelodysplastic syndromes and lymphoid malignancies, their precise role in treatment of these different entities remain to be elucidated. Successful development of these compounds as elements of novel targeted treatment strategies for leukemia will require that clinical studies be performed in conjunction with translational research including efforts to identify predictive biomarkers

Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health: progress towards Sustainable Development Goal 3

Background: Sustainable Development Goal (SDG) 3 aims to “ensure healthy lives and promote well-being for all at all ages”. While a substantial effort has been made to quantify progress towards SDG3, less research has focused on tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas of SDG3, examine the association between outcomes and financing, and identify where resource gains are most needed to achieve the SDG3 indicators for which data are available. Methods: We estimated domestic health spending, disaggregated by source (government, out-of-pocket, and prepaid private) from 1995 to 2017 for 195 countries and territories. For disease-specific health spending, we estimated spending for HIV/AIDS and tuberculosis for 135 low-income and middle-income countries, and malaria in 106 malaria-endemic countries, from 2000 to 2017. We also estimated development assistance for health (DAH) from 1990 to 2019, by source, disbursing development agency, recipient, and health focus area, including DAH for pandemic preparedness. Finally, we estimated future health spending for 195 countries and territories from 2018 until 2030. We report all spending estimates in inflation-adjusted 2019 US$, unless otherwise stated. Findings: Since the development and implementation of the SDGs in 2015, global health spending has increased, reaching$7·9 trillion (95% uncertainty interval 7·8–8·0) in 2017 and is expected to increase to $11·0 trillion (10·7–11·2) by 2030. In 2017, in low-income and middle-income countries spending on HIV/AIDS was$20·2 billion (17·0–25·0) and on tuberculosis it was $10·9 billion (10·3–11·8), and in malaria-endemic countries spending on malaria was$5·1 billion (4·9–5·4). Development assistance for health was $40·6 billion in 2019 and HIV/AIDS has been the health focus area to receive the highest contribution since 2004. In 2019,$374 million of DAH was provided for pandemic preparedness, less than 1% of DAH. Although spending has increased across HIV/AIDS, tuberculosis, and malaria since 2015, spending has not increased in all countries, and outcomes in terms of prevalence, incidence, and per-capita spending have been mixed. The proportion of health spending from pooled sources is expected to increase from 81·6% (81·6–81·7) in 2015 to 83·1% (82·8–83·3) in 2030. Interpretation: Health spending on SDG3 priority areas has increased, but not in all countries, and progress towards meeting the SDG3 targets has been mixed and has varied by country and by target. The evidence on the scale-up of spending and improvements in health outcomes suggest a nuanced relationship, such that increases in spending do not always results in improvements in outcomes. Although countries will probably need more resources to achieve SDG3, other constraints in the broader health system such as inefficient allocation of resources across interventions and populations, weak governance systems, human resource shortages, and drug shortages, will also need to be addressed. Funding: The Bill & Melinda Gates Foundatio

Targeting Huntington’s disease through histone deacetylases

Huntington’s disease (HD) is a debilitating neurodegenerative condition with significant burdens on both patient and healthcare costs. Despite extensive research, treatment options for patients with this condition remain limited. Aberrant post-translational modification (PTM) of proteins is emerging as an important element in the pathogenesis of HD. These PTMs include acetylation, phosphorylation, methylation, sumoylation and ubiquitination. Several families of proteins are involved with the regulation of these PTMs. In this review, I discuss the current evidence linking aberrant PTMs and/or aberrant regulation of the cellular machinery regulating these PTMs to HD pathogenesis. Finally, I discuss the evidence suggesting that pharmacologically targeting one of these protein families the histone deacetylases may be of potential therapeutic benefit in the treatment of HD

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study

BACKGROUND: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria. METHODS: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced. RESULTS: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes. CONCLUSIONS: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700