Acute respiratory infections (ARI) are the leading cause of burden of disease worldwide and have been causally linked with exposure to pollutants from domestic biomass fuels in developing countries. We used longitudinal health data coupled with detailed monitoring and estimation of personal exposure from more than 2 years of field measurements in rural Kenya to estimate the exposure-response relationship for particulates < 10 microm diameter (PM(10)) generated from biomass combustion. Acute respiratory infections and acute lower respiratory infections are concave, increasing functions of average daily exposure to PM(10), with the rate of increase declining for exposures above approximately 1,000-2,000 microg/m(3). This first estimation of the exposure-response relationship for the high-exposure levels characteristic of developing countries has immediate and important consequences for international public health policies, energy and combustion research, and technology transfer efforts that affect more than 2 billion people worldwide.

Acute and chronic respiratory diseases, which are causally linked to exposure to indoor air pollution in developing countries, are the leading cause of global morbidity and mortality. Efforts to develop effective intervention strategies and detailed quantification of the exposure-response relationship for indoor particulate matter require accurate estimates of exposure. We used continuous monitoring of indoor air pollution and individual time-activity budget data to construct detailed profiles of exposure for 345 individuals in 55 households in rural Kenya. Data for analysis were from two hundred ten 14-hour days of continuous real-time monitoring of concentrations of particulate matter [less than/equal to] 10 microm in aerodynamic diameter and the location and activities of household members. These data were supplemented by data on the spatial dispersion of pollution and from interviews. Young and adult women had not only the highest absolute exposure to particulate matter (2, 795 and 4,898 microg/m(3) average daily exposure concentrations, respectively) but also the largest exposure relative to that of males in the same age group (2.5 and 4.8 times, respectively). Exposure during brief high-intensity emission episodes accounts for 31-61% of the total exposure of household members who take part in cooking and 0-11% for those who do not. Simple models that neglect the spatial distribution of pollution within the home, intense emission episodes, and activity patterns underestimate exposure by 3-71% for different demographic subgroups, resulting in inaccurate and biased estimations. Health and intervention impact studies should therefore consider in detail the critical role of exposure patterns, including the short periods of intense emission, to avoid spurious assessments of risks and benefits.

Background

The highly selective α2 -adrenoreceptor agonist, dexmedetomidine, exerts neuroprotective, analgesic, anti-inflammatory and sympatholytic properties that may be beneficial for perinatal asphyxia. The optimal safe dose for pre-clinical newborn neuroprotection studies is unknown.

Methods

Following cerebral hypoxia-ischaemia, dexmedetomidine was administered to nine newborn piglets in a de-escalation dose study in combination with hypothermia (whole body cooling to 33.5°C). Dexmedetomidine was administered with a loading dose of 1 μg/kg and maintenance infusion at doses from 10 to 0.6 μg/kg/h. One additional piglet was not subjected to hypoxia-ischaemia. Blood for pharmacokinetic analysis was sampled pre-insult and frequently post-insult. A one-compartment linear disposition model was used to fit data. Population parameter estimates were obtained using non-linear mixed effects modelling.

Results

All dexmedetomidine infusion regimens led to plasma concentrations above those associated with sedation in neonates and children (0.4-0.8 μg/l). Seven out of the nine piglets with hypoxia-ischaemia experienced periods of bradycardia, hypotension, hypertension and cardiac arrest; all haemodynamic adverse events occurred in piglets with plasma concentrations greater than 1 μg/l. Dexmedetomidine clearance was 0.126 l/kg/h [coefficient of variation (CV) 46.6.%] and volume of distribution was 3.37 l/kg (CV 191%). Dexmedetomidine clearance was reduced by 32.7% at a temperature of 33.5°C. Dexmedetomidine clearance was reduced by 55.8% following hypoxia-ischaemia.

Conclusions

Dexmedetomidine clearance was reduced almost tenfold compared with adult values in the newborn piglet following hypoxic-ischaemic brain injury and subsequent therapeutic hypothermia. Reduced clearance was related to cumulative effects of both hypothermia and exposure to hypoxia. High plasma levels of dexmedetomidine were associated with major cardiovascular complications.

Background: Estimating the burden of disease attributable to long-term exposure to fine particulate matter (PM2.5) in ambient air requires knowledge of both the shape and magnitude of the relative risk (RR) function. However, adequate direct evidence to id

Background The highly selective α2-adrenoreceptor agonist, dexmedetomidine, exerts neuroprotective, analgesic, anti-inflammatory and sympatholytic properties that may be beneficial for perinatal asphyxia. The optimal safe dose for pre-clinical newborn neuroprotection studies is unknown. Methods Following cerebral hypoxia-ischaemia, dexmedetomidine was administered to nine newborn piglets in a de-escalation dose study in combination with hypothermia (whole body cooling to 33.5C). Dexmedetomidine was administered with a loading dose of 1μg/kg and maintenance infusion at doses from 10 to 0.6μg/kg/h. One additional piglet was not subjected to hypoxia-ischaemia. Blood for pharmacokinetic analysis was sampled pre-insult and frequently post-insult. A one-compartment linear disposition model was used to fit data. Population parameter estimates were obtained using non-linear mixed effects modelling. Results All dexmedetomidine infusion regimens led to plasma concentrations above those associated with sedation in neonates and children (0.4-0.8μg/l). Seven out of the nine piglets with hypoxia-ischaemia experienced periods of bradycardia, hypotension, hypertension and cardiac arrest; all haemodynamic adverse events occurred in piglets with plasma concentrations greater than 1μg/l. Dexmedetomidine clearance was 0.126l/kg/h [coefficient of variation (CV) 46.6.%] and volume of distribution was 3.37l/kg (CV 191%). Dexmedetomidine clearance was reduced by 32.7% at a temperature of 33.5C. Dexmedetomidine clearance was reduced by 55.8% following hypoxia-ischaemia. Conclusions Dexmedetomidine clearance was reduced almost tenfold compared with adult values in the newborn piglet following hypoxic-ischaemic brain injury and subsequent therapeutic hypothermia. Reduced clearance was related to cumulative effects of both hypothermia and exposure to hypoxia. High plasma levels of dexmedetomidine were associated with major cardiovascular complications. © 2014 The Authors. The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.