Bacterial meningitis in the African meningitis belt remains 1 of the most serious threats to health. The perceptions regarding meningitis in local populations and the cost of illness for households ...are not well described. We conducted an anthropologic and economic study in Burkina Faso, in the heart of the meningitis belt. Respondents reported combining traditional and modern beliefs regarding disease etiology, which in turn influenced therapeutic care-seeking behavior. Households spent US $90 per meningitis case, or 34% of the annual gross domestic product per capita, and up to US $154 more when meningitis sequelae occurred. Much of this cost was attributable to direct medical expenses, which in theory are paid by the government. Preventive immunization against meningitis will overcome limitations imposed by traditional beliefs and contribute to poverty reduction goals.
Abstract The introduction of new vaccines with much higher prices than traditional vaccines results in increasing budgetary pressure on immunization programs in GAVI-eligible countries, increasing ...the need to ensure their financial sustainability. In this context, the third EPIVAC (Epidemiology and Vaccinology) technical conference was held from February 16 to 18, 2012 at the Regional Institute of Public Health in Ouidah, Benin. Managers of ministries of health and finance from 11 West African countries (GAVI eligible countries), as well as former EPIVAC students and European experts, shared their knowledge and best practices on immunization financing at district and country level. The conference concluded by stressing five major priorities for the financial sustainability of national immunization programs (NIPs) in GAVI-eligible countries. - Strengthen public financing by increasing resources and fiscal space, improving budget processes, increasing contribution of local governments and strengthen efficiency of budget spending. - Promote equitable community financing which was recognized as a significant and essential contribution to the continuity of EPI operations. - Widen private funding by exploring prospects offered by sponsorship through foundations dedicated to immunization and by corporate social responsibility programs. - Contain the potential crowding-out effect of GAVI co-financing and ensure that decisions on new vaccine introductions are evidence-based. - Seek out innovative financing mechanisms such as taxes on food products or a national solidarity fund.
B. Grassi, M. Marzorati, B. Kayser, M. Bordini, A. Colombini, M. Conti, C. Marconi and P. Cerretelli
Instituto di Tecnologie Biomediche Avanzate, Consiglio Nazionale delle Ricerche, Milan, Italy.
...Peak blood lactate (Lablpeak) and blood lactate concentration (Labl)
vs. workload (W) relationships during acclimatization to altitude and in
the deacclimatization were evaluated in 10 Caucasian lowlanders at sea
level (SL0); after approximately 1 wk (Alt1wk), 3 wk (Alt3wk), and 5 wk
(Alt5wk) at 5,050 m; and weekly during the first 5 wk after return to sea
level (SL1wk-SL5wk). Incremental bicycle ergometer exercises (30 W added
every 4 min up to exhaustion) were performed. At Alt1wk and at Alt5wk, the
experiments were repeated in hypobaric normoxia (Alt1wk-O2 and Alt5wk-O2).
Labl was determined at rest and during the last approximately 30 s of
each W. Lablpeak was taken as the highest Labl during recovery.
Acid-base status (pH and concentration of HCO-3 in arterialized capillary
blood) was determined at rest. Mean Lablpeak values were 11.5 (SL0), 8.0
(Alt1wk), 6.4 (Alt3wk), 6.3 (Alt5wk), 8.0 (SL1wk), 9.4 (SL2wk), 10.8
(SL3wk), 11.3 (SL4wk), and 11.6 (SL5wk) mM. At Alt1wk-O2 and Alt5wk-O2,
peak W increased, compared with Alt1wk and Alt5wk, whereas no changes were
observed for Lablpeak. Labl vs. W was shifted to the left (i.e., higher
Labl values were found for the same W) at Alt1wk compared with SL0 and
partially shifted back to the right (i.e., lower Labl values were found
for the same W) at Alt3wk and Alt5wk. At Alt1wk-O2 and Alt5wk-O2, Labl
vs. W values were superimposed on that at SL0. At SL1wk-SL5wk, Labl vs. W
values were shifted to the right compared with that at SL0. At Alt1wk, a
condition of respiratory alkalosis was found, which was only partially
compensated for during acclimatization. At SL1wk, the acid-base status was
back to normal. We conclude that 1) the reduced Lablpeak at altitude is
still present for 2-3 wk after return from altitude; is not attributable to
reduced peak W nor to hypoxia per se, nor to a reduced buffer capacity;
alternatively, it could be related to some central determinants of fatigue.
2) The Labl vs. W leftward shift at altitude was due to hypoxia per se.
3) The factor(s) responsible for the Labl vs. W partial rightward shift
during acclimatization could still be effective during the first weeks
after return to sea level.
Department of Pediatric Hematology-Oncology, University of Milano-Bicocca, S. Gerardo Hospital, Monza, Italy. carmelo.rizzari@pediatriamonza.it
BACKGROUND AND OBJECTIVES: Pegylated-asparaginase ...(PEG-ASP) has been traditionally used as a second-line preparation in children with acute lymphoblastic leukemia (ALL) presenting with clinical allergy to native asparaginase (ASP) products. The main goal of the present study was to investigate the pharmacological effects of the administration of PEG-ASP given as a first-line product in children with ALL. DESIGN AND METHODS: PEG-ASP serum enzymatic activity and serum and cerebrospinal fluid (CSF) levels of asparagine were investigated in 20 children with newly diagnosed ALL enrolled in the ongoing AIEOP ALL 2000 protocol and treated with PEG-ASP as a first-line ASP preparation. During induction the drug was administered at the dosage of 1,000 U/m2 i.v. on days 12 and 27. During reinduction the drug was administered only once at the same dosage. RESULTS: Among the 20 patients treated in induction serum PEG-ASP activity equalled or exceeded 100 U/L in 18/18, 11/11 and 15/18 of the samples available on days 22, 25 and 27, respectively, and in 16/16, 12/15 and 5/8 samples available on days 36, 39 and 45, respectively. In the 15 patients treated during reinduction serum PEG-ASP activity > or =100 U/L was observed in 14/15, 11/14, 6/10, and 0/12 samples available on days 11, 15, 18 and 23, respectively, after the administration of the drug. Serum asparagine levels were below the detection limit (
OBJECTIVE:To analyze the behavior of total creatine kinase (CK) and other muscular damage markers and to compare CK activity and renal function indices in professional cyclists during a 3-week stage ...race.
DESIGN:Prospective, noncomparative, interventional.
SETTING:The athletes were recruited during the 2011 Giro dʼItalia.
PARTICIPANTS:Nine professional road cyclists from the Liquigas-Cannondale team and competing in the race.
ASSESSMENT OF RISK FACTORS:Blood samples were collected on the day before the start of the race, on day 12, and on the final day (day 22) of the race.
MAIN OUTCOME MEASURES:Creatinine and cystatin C concentrations, CK, lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) activities were measured. The estimated glomerular filtration rate was calculated according to equations based on creatinine, cystatin C, or both.
RESULTS:Creatine kinase and AST activity increased during the second part of the race, and LDH activity progressively increased during the entire course of the race. There was a negative correlation between CK activity and the delta prerace-day 12 of glomerular filtration rate, as obtained with simple cystatin C or with Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine and cystatin C equations.
CONCLUSIONS:The effect of prolonged strenuous muscular effort on biochemical laboratory parameters in professional road cyclists was confirmed. The correlation observed between renal function and CK activity underscores that measurement of cystatin C is more accurate than creatinine alone in the evaluation of renal function and that it is unaffected by response to physical stress–induced muscular damage.
Calcium and phosphate are essential for cell functions, and their serum concentrations result from the balance between intestinal absorption, bony storage, and urinary excretion. Fibroblast growth ...factor 23 (
FGF23
), expressed by osteocytes and osteoblasts, acts in the kidney, leading to hypophosphatemia and low 1,25‐dihydroxycholecalciferol synthesis, but suppresses parathyroid function. The aim of this study was to explore the effects of a high‐energy demanding cycling race on this bone–kidney–parathyroid axis. We studied nine cyclists during the 2011
G
iro d'
I
talia
stage race. Pre‐analytical and analytical phases followed academic and anti‐doping recommendations. Serum parathyroid hormone (
PTH
), 25(
OH
)
D
, total calcium, inorganic phosphorus, and plasma
FGF23
were measured on days −1, 12, and 22 and corrected for changes in plasma volume. Dietary calcium and phosphorus, anthropometric parameters (height, weight, and body mass index) and indexes of metabolic effort (net energy expenditure, power output) were recorded. Dietary calcium and phosphorus intakes were kept at the same levels throughout the race. Twenty‐five (
OH
)
D
,
PTH
, and calcium concentrations remained stable.
FGF23
increased 50% with a positive correlation with the indexes of metabolic effort and, consequently, phosphorous decreased, although only in the first half. The strong metabolic effort acts on the bone–kidney–parathyroid system, and the rise in
FGF23
plasma concentration might be aimed at maintaining calcium and phosphorus homeostasis.
Background:
In this ongoing phase 2, open‐label study in pediatric pts with newly‐diagnosed (ND) or imatinib/dasatinib (IMA/DAS) resistant/intolerant (R/I) CML (NCT01077544), oral NIL 230 mg/m2 BID ...(rounded to nearest 50 mg; maximum dose 400 mg BID) was efficacious following 12, 28‐day treatment cycles, with no unexpected adverse event (AE) findings so far (Hijiya et al. Pediatr Blood Cancer 2017;64: e26772).
Aims:
To analyze the safety and tolerability of NIL in pediatric pts based on a longer follow‐up after 36 cycles of treatment.
Methods:
Eligible pts (1–<18 years) had CML in chronic or accelerated phase (CP/AP) R/I to IMA/DAS, or were ND with CML‐CP. Pts have been on NIL for ≥36 cycles of 28‐day treatment, or have discontinued treatment. Safety and tolerability assessments included incidence and severity of AEs, physical examinations and laboratory tests. Growth and sexual development were also assessed.
Results:
Fifty‐eight pts (R/I, n = 33; ND, n = 25) were enrolled and received NIL. No pts with CML‐AP enrolled. Median age was 13 years (range: 2–17) in the R/I to IMA/DAS cohort and 13 years (range: 10–16) in the ND cohort. At the data cut‐off (11 April 2018), median duration of exposure to NIL was 33 months (range: 0.5–55) in the R/I to IMA/DAS cohort and 33 months (range: 0.7–54) in the ND cohort. Safety results are shown in the Table. The most frequent all‐grade AEs occurring in the overall pt population were headache (44.8%), pyrexia (37.9%), increased alanine aminotransferase (ALT; 34.5%) and increased blood bilirubin (34.5%). The most common serious AEs were viral gastroenteritis, pyrexia, and viral infection (3.4% each). In total, 13 pts had ≥1 AE that led to treatment discontinuation; the most frequent of these were increased blood bilirubin (n = 3), hyperbilirubinemia (n = 3) and rash (n = 2). Assessment of AEs of special interest (AESIs) (Table) showed no clinical cardiovascular events. No grade 3/4 QT prolongation occurred. Grade 1/2 QT prolongation (≤500 msec and no signs/symptoms of arrhythmia) resolved in 9/9 pts; 6/9 pts required dose adjustment, in 2/9 pts the AE was considered serious and in 1 pt the AE was suspected to be related to NIL. Hepatic transaminase and bilirubin elevations were observed in 36 (62.1%) pts. Six pts had concomitant elevation of ALT >3 × ULN and bilirubin >2 × ULN, with alkaline phosphatase ≤2 × ULN. Bilirubin increase was mainly driven by unconjugated bilirubin and was consistent with the UGT1A1 inhibition by NIL. Grade 3/4 AESIs in the R/I to IMA/DAS and ND arms, respectively, included: hepatotoxicity, 24.2% and 24.0%; hepatic transaminase and bilirubin elevations, 21.2% and 24.0%; drug induced liver injury, 3.0% (n = 1, transaminase/bilirubin elevation without signs of severe or progressive liver dysfunction) and 0%; rash, 15.2% and 8.0%; and myelosuppression, 0% and 12.0%. No pt died while on treatment; one pt in the R/I to IMA/DAS cohort died due to disease progression during survival follow‐up. In assessments of growth and development, 7 (12.1%) pts experienced a decrease of two main height percentile lines when last available height was compared with baseline; no trend was seen in assessment of BMI, bone age, bone biomarkers, or sexual maturation.
Summary/Conclusion:
The safety profile of NIL in this 36‐cycle safety update was consistent with previously reported results and with the known AE profile of NIL in adults treated with 400 mg BID. AEs were manageable with monitoring and dose modification. A trend towards growth deceleration over time was identified, which warrants further observation.
This collection of original articles and surveys addresses the recent advances in linear and nonlinear aspects of the theory of partial differential equations. The key topics include operators as ...'sums of squares' of real and complex vector fields, nonlinear evolution equations, local solvability, and hyperbolic questions. Contributors: Ambrosio, Berhanu, J.-M. Bony, Chemin, Dencker, Gallagher, Gerard, Hounie, Jannelli, Kajitani, Lerner, Nishitani, Petkov, Rauch, Reissig, Spagnolo, Tataru, Treves, Uhlmann, and Zuazua.
Tibetan highlanders develop at altitude peak aerobic power levels close to those of Caucasians at sea level. In order to establish whether this feature is genetic and, as a consequence, retained
by ...Tibetan lowlanders, altitude-induced changes of peak aerobic performance were assessed in four groups of volunteers with different ethnic, altitude exposure and fitness characteristics, i.e. eight
untrained second-generation Tibetans (Tib 2) born and living at 1300 m; seven altitude Sherpas living at â¼2800â3500 m; and
10 untrained and five trained Caucasians. Measurements were carried out at sea level or at Kathmandu (1300 m, Nepal) (PRE),
and after 2â4 (ALT1), 14â16 (ALT2), and 26â28 (ALT3) days at 5050 m. At ALT3, of untrained and trained Caucasians was â31% and â46%, respectively. By contrast, of Tib 2 and Sherpas was â8% and â15%, respectively. At ALT3, peak heart rate (HR peak ) of untrained and trained Caucasians was 148 ± 11 and 149 ± 7 beats min â1 , respectively; blood oxygen saturation at peak exercise was 76 ± 6% and 73 ± 6%, and haemoglobin concentration (Hb) was 19.4 ± 1.0 and 18.6 ± 1.2 g dl â1 , respectively. Compared to Caucasians, Tib 2 and Sherpas exhibited at ALT3 higher HR peak (179 ± 9 and 171 ± 4 beats min â1 , P < 0.001), lower Hb (16.6 ± 0.6 and 17.4 ± 0.9 g dl â1 , respectively, P < 0.001), and slightly but non-significantly greater average values (82 ± 6 and 80 ± 7%). The above findings and the time course of adjustment of the investigated variables suggest that
Tibetan lowlanders acclimatize to chronic hypoxia more quickly than Caucasians, independent of the degree of fitness of the
latter.
PDF
