Tapentadol Prolonged Release for Long-Term Treatment of Pain in Children

Purpose: Investigation of the efficacy and safety of tapentadol prolonged release (PR) compared with morphine PR for long-term treatment of pain in children. / Patients and Methods: Children aged 6 to < 18 years requiring long-term treatment with opioids were studied in a 12-month, 2-part, multi-center trial: Part 1, 14-day open-label, randomized, active-controlled, parallel group non-inferiority trial comparing twice daily tapentadol PR with morphine PR; Part 2, open-label treatment with tapentadol PR for up to 12 months or no treatment “safety observation period”. Pain intensity was rated with visual analogue scale or Faces Pain Scale-Revised, and non-inferiority was assessed by comparison of “treatment responders” (those completing the 14-day treatment period and showing pre-defined changes in pain rating) in each group. / Results: Twenty-three of 48 centers enrolled 73 patients. In Part 1, 45 and 24 patients received tapentadol or morphine, respectively, of which 40 and 22 completed 14-day treatment. In Part 2, thirty-six and 58 patients entered the tapentadol PR or observation periods, respectively, with 20/36 completing at least 12 weeks of treatment; 10 of the 36 had received morphine in Part 1. Forty-four of the 58 patients in the safety observation period had received tapentadol. Tapentadol PR was non-inferior to morphine PR (lower limit of confidence interval above negative non-inferiority margin of − 0.2) in Part 1. Rates of adverse events were as expected with nausea (22.2%) and constipation (15.6%) in the tapentadol PR group, and with vomiting (33.3%), nausea and constipation (each 16.7%) in the morphine PR group. No new safety issues were identified; the safety profile of tapentadol over the 12 months treatment and observation periods was comparable to that established in subjects > 18 years old. / Conclusion: Tapentadol PR was well tolerated and equivalent to morphine PR for both efficacy and safety in children (6 to < 18 years old) requiring long-term treatment with opioids

Global atmospheric budget of acetaldehyde: 3-D model analysis and constraints from in-situ and satellite observations

We construct a global atmospheric budget for acetaldehyde using a 3-D model of atmospheric chemistry (GEOS-Chem), and use an ensemble of observations to evaluate present understanding of its sources and sinks. Hydrocarbon oxidation provides the largest acetaldehyde source in the model (128 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;, a factor of 4 greater than the previous estimate), with alkanes, alkenes, and ethanol the main precursors. There is also a minor source from isoprene oxidation. We use an updated chemical mechanism for GEOS-Chem, and photochemical acetaldehyde yields are consistent with the Master Chemical Mechanism. We present a new approach to quantifying the acetaldehyde air-sea flux based on the global distribution of light absorption due to colored dissolved organic matter (CDOM) derived from satellite ocean color observations. The resulting net ocean emission is 57 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;, the second largest global source of acetaldehyde. A key uncertainty is the acetaldehyde turnover time in the ocean mixed layer, with quantitative model evaluation over the ocean complicated by known measurement artifacts in clean air. Simulated concentrations in surface air over the ocean generally agree well with aircraft measurements, though the model tends to overestimate the vertical gradient. PAN:NO&lt;sub&gt;x&lt;/sub&gt; ratios are well-simulated in the marine boundary layer, providing some support for the modeled ocean source. We introduce the Model of Emissions of Gases and Aerosols from Nature (MEGANv2.1) for acetaldehyde and ethanol and use it to quantify their net flux from living terrestrial plants. Including emissions from decaying plants the total direct acetaldehyde source from the land biosphere is 23 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;. Other terrestrial acetaldehyde sources include biomass burning (3 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;) and anthropogenic emissions (2 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;). Simulated concentrations in the continental boundary layer are generally unbiased and capture the spatial gradients seen in observations over North America, Europe, and tropical South America. However, the model underestimates acetaldehyde levels in urban outflow, suggesting a missing source in polluted air. Ubiquitous high measured concentrations in the free troposphere are not captured by the model, and based on present understanding are not consistent with concurrent measurements of PAN and NO&lt;sub&gt;x&lt;/sub&gt;: we find no compelling evidence for a widespread missing acetaldehyde source in the free troposphere. We estimate the current US source of ethanol and acetaldehyde (primary + secondary) at 1.3 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt; and 7.8 Tg a&lt;sup&gt;&amp;minus;1&lt;/sup&gt;, approximately 60{%} and 480% of the corresponding increases expected for a national transition from gasoline to ethanol fuel

Chemistry, transport and dry deposition of trace gases in the boundary layer over the tropical Atlantic Ocean and the Guyanas during the GABRIEL field campaign

We present a comparison of different Lagrangian and chemical box model calculations with measurement data obtained during the GABRIEL campaign over the tropical Atlantic Ocean and the Amazon rainforest in the Guyanas, October 2005. Lagrangian modelling of boundary layer (BL) air constrained by measurements is used to derive a horizontal gradient (&amp;asymp;5.6 pmol/mol km&lt;sup&gt;&amp;minus;1&lt;/sup&gt;) of CO from the ocean to the rainforest (east to west). This is significantly smaller than that derived from the measurements (16&amp;ndash;48 pmol/mol km&lt;sup&gt;&amp;minus;1&lt;/sup&gt;), indicating that photochemical production from organic precursors alone cannot explain the observed strong gradient. It appears that HCHO is overestimated by the Lagrangian and chemical box models, which include dry deposition but not exchange with the free troposphere (FT). The relatively short lifetime of HCHO implies substantial BL-FT exchange. The mixing-in of FT air affected by African and South American biomass burning at an estimated rate of 0.12 h&lt;sup&gt;&amp;minus;1&lt;/sup&gt; increases the CO and decreases the HCHO mixing ratios, improving agreement with measurements. A mean deposition velocity of 1.35 cm/s for H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; over the ocean as well as over the rainforest is deduced assuming BL-FT exchange adequate to the results for CO. The measured increase of the organic peroxides from the ocean to the rainforest (&amp;asymp;0.66 nmol/mol d&lt;sup&gt;&amp;minus;1&lt;/sup&gt;) is significantly overestimated by the Lagrangian model, even when using high values for the deposition velocity and the entrainment rate. Our results point at either heterogeneous loss of organic peroxides and/or their radical precursors, underestimated photodissociation or missing reaction paths of peroxy radicals not forming peroxides in isoprene chemistry. We calculate a mean integrated daytime net ozone production (NOP) in the BL of (0.2&amp;plusmn;5.9) nmol/mol (ocean) and (2.4&amp;plusmn;2.1) nmol/mol (rainforest). The NOP strongly correlates with NO and has a positive tendency in the boundary layer over the rainforest

Hydroxyl radicals in the tropical troposphere over the Suriname rainforest: airborne measurements

Direct measurements of OH and HO&lt;sub&gt;2&lt;/sub&gt; over a tropical rainforest were made for the first time during the GABRIEL campaign in October 2005, deploying the custom-built HORUS instrument (HydrOxyl Radical measurement Unit based on fluorescence Spectroscopy), adapted to fly in a Learjet wingpod. Biogenic hydrocarbon emissions were expected to strongly reduce the OH and HO&lt;sub&gt;2&lt;/sub&gt; mixing ratios as the air is transported from the ocean over the forest. However, surprisingly high mixing ratios of both OH and HO&lt;sub&gt;2&lt;/sub&gt; were encountered in the boundary layer over the rainforest. &lt;br&gt;&lt;br&gt; The HORUS instrumentation and calibration methods are described in detail and the measurement results obtained are discussed. The extensive dataset collected during GABRIEL, including measurements of many other trace gases and photolysis frequencies, has been used to quantify the main sources and sinks of OH. Comparison of these measurement-derived formation and loss rates of OH indicates strong previously overlooked recycling of OH in the boundary layer over the tropical rainforest, occurring in chorus with isoprene emission

Hydroxyl radicals in the tropical troposphere over the Suriname rainforest: airborne measurements

Direct measurements of OH and HO&lt;sub&gt;2&lt;/sub&gt; over a tropical rainforest were made for the first time during the GABRIEL campaign in October 2005, deploying the custom-built HORUS instrument (HydrOxyl Radical measurement Unit based on fluorescence Spectroscopy), adapted to fly in a Learjet wingpod. Biogenic hydrocarbon emissions were expected to strongly reduce the OH and HO&lt;sub&gt;2&lt;/sub&gt; mixing ratios as the air is transported from the ocean over the forest. However, surprisingly high mixing ratios of both OH and HO&lt;sub&gt;2&lt;/sub&gt; were encountered in the boundary layer over the rainforest. &lt;br&gt;&lt;br&gt; The HORUS instrumentation and calibration methods are described in detail and the measurement results obtained are discussed. The extensive dataset collected during GABRIEL, including measurements of many other trace gases and photolysis frequencies, has been used to quantify the main sources and sinks of OH. Comparison of these measurement-derived formation and loss rates of OH indicates strong previously overlooked recycling of OH in the boundary layer over the tropical rainforest, occurring in chorus with isoprene emission

Hydroxyl radicals in the tropical troposphere over the Suriname rainforest: comparison of measurements with the box model MECCA

As a major source region of the hydroxyl radical OH, the Tropics largely control the oxidation capacity of the atmosphere on a global scale. However, emissions of hydrocarbons from the tropical rainforest that react rapidly with OH can potentially deplete the amount of OH and thereby reduce the oxidation capacity. The airborne GABRIEL field campaign in equatorial South America (Suriname) in October 2005 investigated the influence of the tropical rainforest on the HOx budget (HOx = OH + HO2). The first observations of OH and HO2 over a tropical rainforest are compared to steady state concentrations calculated with the atmospheric chemistry box model MECCA. The important precursors and sinks for HOx chemistry, measured during the campaign, are used as constraining parameters for the simulation of OH and HO2. Significant underestimations of HOx are found by the model over land during the afternoon, with mean ratios of observation to model of 12.2 ± 3.5 and 4.1 ± 1.4 for OH and HO2, respectively. The discrepancy between measurements and simulation results is correlated to the abundance of isoprene. While for low isoprene mixing ratios (above ocean or at altitudes \u3e3 km), observation and simulation agree fairly well, for mixing ratios \u3e200 pptV (rainforest) the model tends to underestimate the HOx observations as a function of isoprene. Box model simulations have been performed with the condensed chemical mechanism of MECCA and with the detailed isoprene reaction scheme of MCM, resulting in similar results for HOx concentrations. Simulations with constrained HO2 concentrations show that the conversion from HO2 to OH in the model is too low. However, by neglecting the isoprene chemistry in the model, observations and simulations agree much better. An OH source similar to the strength of the OH sink via isoprene chemistry is needed in the model to resolve the discrepancy. A possible explanation is that the oxidation of isoprene by OH not only dominates the removal of OH but also produces it in a similar amount. Several additional reactions which directly produce OH have been implemented into the box model, suggesting that upper limits in producing OH are still not able to reproduce the observations (improvement by factors of ≈2.4 and ≈2 for OH and HO2, respectively). We determine that OH has to be recycled to 94% instead of the simulated 38% to match the observations, which is most likely to happen in the isoprene degradation process, otherwise additional sources are required

SARS-CoV-2 infections and impact of the COVID-19 pandemic in pregnancy and breastfeeding: Results from an observational study in primary care in Belgium

COVID-19 also affects pregnant and breastfeeding women. Hence, clinicians and policymakers require reliable evidence on COVID-19 epidemiology and consequences in this population. We aimed to assess the susceptibility of pregnant women to SARS-CoV-2 and women’s perceived impact of the pandemic on their breastfeeding practices, medical counseling and social support. We performed a cross-sectional study using an online survey in primary care in Belgium. Pregnant and breastfeeding women and women who breastfed in the preceding four weeks were eligible to participate. The survey was distributed through social media in April 2020. In total, 6470 women participated (i.e., 2647 pregnant and 3823 breastfeeding women). Overall, 0.3% of all respondents reported to have tested positive for SARS-CoV-2, not indicating a higher susceptibility of pregnant women to contracting COVID-19. More than 90% refuted that the pandemic affected their breastfeeding practices, nor indicated that the coronavirus was responsible for breastfeeding cessation. Half of the women even considered giving longer breastmilk because of the coronavirus. In contrast, women’s medical counseling and social support were negatively affected by the lockdown. Women without previous breastfeeding experience and in the early postpartum period experienced a higher burden in terms of reduced medical counseling and support. In the future, more consideration and alternative supportive measures such as tele-visits by midwives or perinatal organizations are required for these women

Predicting hospital admission and discharge with symptom or function scores in patients with schizophrenia: pooled analysis of a clinical trial extension

<p>Abstract</p> <p>Background</p> <p>The purpose of this analysis was to evaluate relationships between hospital admission or discharge and scores for symptom or functioning in patients with schizophrenia.</p> <p>Methods</p> <p>Data were from three 52-week open-label extensions of the double-blind pivotal trials of paliperidone extended-release (ER). Symptoms and patient function were measured every 4 weeks using the Personal and Social Performance (PSP) scale and the Positive and Negative Syndrome Scale (PANSS). The intent-to-treat analysis set was defined as open-label patients who had at least one post-baseline PSP and PANSS measurement. Time until first hospitalization was evaluated using the Cox proportional hazard model with categorical time-dependent measures for the PSP (1 to 30, 31 to 70, 71 to 100) or PANSS (< 75, ≥ 75 to < 95, ≥ 95), as well as age, gender, schizophrenia duration, and country. Similar analyses were performed for time to discharge.</p> <p>Results</p> <p>Of the 1,077 enrolled patients, 1,028 (95.5%) met study criteria; of these, 382 (37.2%) were hospitalized at open-label baseline. Compared with patients with PSP ≥ 71 group, the hazard for new hospitalization was 8.351 times greater (<it>P </it>= 0.0001) for patients with the poorest functioning (PSP 1 to 30) and 1.977 times greater (<it>P </it>= 0.0295) for patients with PSP of 31-70 compared to the ≥ 71 group. The hazard for new hospitalization was 5.457 times greater (<it>P </it>< 0.0001) for patients PANSS ≥ 95 and 2.316 times greater (<it>P </it>= 0.0027) for the ≥ 75 to < 95 group compared with the < 75 group. For patients hospitalized at baseline, the PANSS ≥ 95 patients had a discharge hazard that was 0.456 times lower than for the < 75 patients (<it>P </it>< 0.0001). The hazard for discharge was 0.646 times lower (<it>P = </it>0.0012) for the PANSS ≥ 75 to < 95 group compared with the < 75 group. A patient's country was a significant predictor variable, with US patients being admitted and discharged faster.</p> <p>Conclusions</p> <p>Better functioning or being less symptomatic is associated with reduced risk for hospitalization and greater chance for early discharge. Treatments or programs that reduce symptoms or improve function decrease the risk of hospitalization in community patients or increase the chance of discharge for hospitalized patients.</p