Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis.

The risk of adverse effects of nitrous oxide (N2O) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with N2O exposure in medical and recreational settings. We calculated the pooled estimates for the studied outcomes and assessed the potential bias related to population stratification using principal component analysis. Eighty-five publications met the inclusion criteria and reported on 100 patients with a median age of 27 years and 57% of recreational users. The most frequent outcomes were subacute combined degeneration (28%), myelopathy (26%), and generalized demyelinating polyneuropathy (23%). A T2 signal hyperintensity in the spinal cord was reported in 68% (57.2-78.8%) of patients. The most frequent clinical manifestations included paresthesia (80%; 72.0-88.0%), unsteady gait (58%; 48.2-67.8%), and weakness (43%; 33.1-52.9%). At least one hematological abnormality was retrieved in 71.7% (59.9-83.4%) of patients. Most patients had vitamin B12 deficiency: vitamin B12 <150 pmol/L (70.7%; 60.7-80.8%), homocysteine >15 µmol/L (90.3%; 79.3-100%), and methylmalonic acid >0.4 µmol/L (93.8%; 80.4-100%). Consistently, 85% of patients exhibited a possibly or probably deficient vitamin B12 status according to the cB12 scoring system. N2O can produce severe outcomes, with neurological or hematological disorders in almost all published cases. More than half of them are reported in the setting of recreational use. The N2O-related burden is dominated by vitamin B12 deficiency. This highlights the need to evaluate whether correcting B12 deficiency would prevent N2O-related toxicity, particularly in countries with a high prevalence of B12 deficiency

Patterns of healthcare seeking among people reporting chronic conditions in rural sub-Saharan Africa: findings from a population-based study in Burkina Faso.

OBJECTIVE: Non-communicable diseases are rapidly becoming one of the leading causes of morbidity and mortality in sub-Saharan Africa. Yet, little is known about patterns of healthcare seeking among people with chronic conditions in these settings. We aimed to explore determinants of healthcare seeking among people who reported at least one chronic condition in rural Burkina Faso. METHODS: Data were drawn from a cross-sectional population-based survey conducted across 24 districts on 52 562 individuals from March to June 2017. We used multinomial logistic regression to assess factors associated with seeking care at a formal provider (facility-based care) or at an informal provider (home and traditional treatment) compared to no care. RESULTS: 1124 individuals (2% of all respondents) reported at least one chronic condition. Among those, 22.8% reported formal care use, 10.6% informal care use, and 66.6% no care. The presence of other household members reporting a chronic condition (RRR = 0.57, 95%-CI [0.39, 0.82]) was negatively associated with seeking formal care. Wealthier households (RRR = 2.14, 95%-CI [1.26, 3.64]), perceived illness severity (RRR = 3.23, 95%-CI [2.22, 4.70]) and suffering from major chronic conditions (RRR = 1.54, 95%-CI [1.13, 2.11]) were positively associated with seeking formal care. CONCLUSION: Only a minority of individuals with chronic conditions sought formal care, with important differences due to socio-economic status. Policies and interventions aimed at increasing the availability and affordability of services for early detection and management in peripheral settings should be prioritised

Fifty years of the CERN Proton Synchrotron : Volume 2

This report sums up in two volumes the first 50 years of operation of the CERN Proton Synchrotron. After an introduction on the genesis of the machine, and a description of its magnet and powering systems, the first volume focuses on some of the many innovations in accelerator physics and instrumentation that it has pioneered, such as transition crossing, RF gymnastics, extractions, phase space tomography, or transverse emittance measurement by wire scanners. The second volume describes the other machines in the PS complex: the proton linear accelerators, the PS Booster, the LEP pre-injector, the heavy-ion linac and accumulator, and the antiproton rings.Comment: 58 pages, published as CERN Yellow Report https://cds.cern.ch/record/1597087?ln=e

Impact of age, leukocyte count and day 21-bone marrow response to chemotherapy on the long-term outcome of children with philadelphia chromosome-positive acute lymphoblastic leukemia in the pre-imatinib era: results of the FRALLE 93 study

<p>Abstract</p> <p>Background</p> <p>We explored the heterogeneity of philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL) in a study of the effect of early features on prognosis in children. Here we report the long-term results of the FRALLE 93 study conducted in the era before the use of tyrosine kinase inhibitors.</p> <p>Methods</p> <p>Between 1993 and 1999, 36 children with Ph1-ALL were enrolled into the FRALLE 93 protocol. After conventional four-drug induction, children were stratified by availability of an HLA-matched sibling.</p> <p>Results</p> <p>Complete remission (CR) was observed in 26 children (72%), of which 13 underwent allogeneic bone marrow transplantation (BMT). Thirty-one children were good responders to prednisone, defined on day 8, and 21 were good responders to chemotherapy, defined by day-21 bone marrow (M1). Overall five-year disease-free survival (DFS) was 42 ± 9.7%. Based on multivariate analysis, two groups showed marked differences in five-year outcome: children with age<10, leukocyte count <100,000/mm³and day-21 M1 marrow had a more favorable prognosis (14 pts: 100% CR, event free survival [EFS]: 57%, overall survival [OS]: 79%), than the high-risk group (22 patients: 55% CR, EFS: 18%, OS: 27%) (p < 0.005). We also observed a non statistically significant difference (p = 0.14) in outcome between these groups for transplanted patients (5-year DFS: 83 ± 14% and 33 ± 15%, respectively).</p> <p>Conclusion</p> <p>Age, leukocyte count and early response to treatment defined by the D21 bone marrow response provide an accurate model for outcome prediction. The combination of available tools such as minimal residual disease assessment with determination of these simple factors could be useful for refining indications for BMT in the current era of tyrosine-kinase inhibitor-based therapy.</p

No impact of performance-based financing on the availability of essential medicines in Burkina Faso: A mixed-methods study

Access to safe, effective, and affordable essential medicines (EM) is critical to quality health services and as such has played a key role in innovative health system strengthening approaches such as Performance-based Financing (PBF). Available literature indicates that PBF can improve EM availability, but has not done so consistently in the past. Qualitative explorations of the reasons are yet scarce. We contribute to expanding the literature by estimating the impact of PBF on EM availability and stockout in Burkina Faso and investigating mechanisms of and barriers to change. The study used an explanatory mixed methods design. The quantitative study component followed a quasi-experimental design (difference-in-differences), comparing how EM availability and stockout had changed three years after implementation in 12 PBF and in 12 control districts. Qualitative data was collected from purposely selected policy and implementation stakeholders at all levels of the health system and community, using in-depth interviews and focus group discussions, and explored using deductive coding and thematic analysis. We found no impact of PBF on EM availability and stockouts in the quantitative data. Qualitative narratives converge in that EM supply had increased as a result of PBF, albeit not fully satisfactorily and sustainably so. Reasons include persisting contextual challenges, most importantly a public medicine procurement monopoly; design challenges, specifically a disconnect and disbalance in incentive levels between service provision and service quality indicators; implementation challenges including payment delays, issues around performance verification, and insufficient implementation of activities to strengthen stock management skills; and concurrently implemented policies, most importantly a national user fee exemption for children and pregnant women half way through the impact evaluation period. The case of PBF and EM availability in Burkina Faso illustrates the difficulty of incentivizing and effecting holistic change in EM availability in the presence of strong contextual constraints and powerful concurrent policies.</jats:p

Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2−/− mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascad

Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods

There is substantial evidence to link what we eat to the reduction of the risk of major chronic diseases and/or the improvement of functions. Thus, it is important for public health agencies and the food industry to facilitate the consumption of foods with particular health benefits by providing consumer products and messages based on scientific evidence. Although fragmentary advice is available from a range of sources, there is a lack of comprehensive scientific guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods. Such guidelines are needed both to support nutrition science in general, and to facilitate the substantiation of health claims. In the present study, which presents the consensus view of an International Life Sciences Institute Europe Expert Group that included senior scientists from academia and industry, the term ‘foods' refers to foods, dietary supplements and food constituents, but not to whole diets. The present study is based on an initial survey of published papers, which identified the range and strengths and weaknesses of current methodologies, and was finalised following exchanges between representatives from industry, academia and regulatory bodies. The major factors involved in the design, conduct and reporting of studies are identified, summarised in a checklist table that is based on the Consolidated Standards of Reporting Trials guidelines, and elaborated and discussed in the tex

Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods

There is substantial evidence to link what we eat to the reduction of the risk of major chronic diseases and/or the improvement of functions. Thus, it is important for public health agencies and the food industry to facilitate the consumption of foods with particular health benefits by providing consumer products and messages based on scientific evidence. Although fragmentary advice is available from a range of sources, there is a lack of comprehensive scientific guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods. Such guidelines are needed both to support nutrition science in general, and to facilitate the substantiation of health claims. In the present study, which presents the consensus view of an International Life Sciences Institute Europe Expert Group that included senior scientists from academia and industry, the term †foods’ refers to foods, dietary supplements and food constituents, but not to whole diets. The present study is based on an initial survey of published papers, which identified the range and strengths and weaknesses of current methodologies, and was finalised following exchanges between representatives from industry, academia and regulatory bodies. The major factors involved in the design, conduct and reporting of studies are identified, summarised in a checklist table that is based on the Consolidated Standards of Reporting Trials guidelines, and elaborated and discussed in the text. © 2011 ILSI Europe