Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Unusual cleavage of phosphaalkynes triple bond in the coordination sphere of transition metals.

The reaction of RCP (R = Me, tBu, iPr) with Co2(CO)8 and Fe2(CO)9 under mild conditions led to unpredictable fragmentations of the CP triple bond and subsequent formation of clusters with a dimeric Co3E (E = P and RC) and an Fe3P(CR) core, respectively.

Coordination Behavior of [Cp″2Zr(µ1:1-As4)] towards Lewis Acids.

The functionalization of the arsenic transfer reagent [Cp″2Zr(η1:1-As4)] (1) focuses on modifying its properties and enabling a broader scope of reactivity. The coordination behavior of 1 towards different Lewis-acidic transition metal complexes and main group compounds is investigated by experimental and computational studies. Depending on the steric requirements of the Lewis acids and the reaction temperature, a variety of new complexes with different coordination modes and coordination numbers could be synthesized. Depending on the Lewis acid (LA) used, a mono-substitution in [Cp″2Zr(µ,η1:1:1:1-As4)(LA)] (LA = Fe(CO)4 (4); B(C6F5)3 (7)) and [Cp″2Zr(µ,η3:1:1-As4)(Fe(CO)3)] (5) or a di-substitution [Cp″2Zr(µ3,η1:1:1:1-As4)(LA)2] (LA = W(CO)5 (2); CpMn(CO)2 (3); AlR3 (6, R = Me, Et, iBu)) are monitored. In contrast to other coordination products, 5 shows an η3 coordination in which the butterfly As4 ligand is rearranged to a cyclo-As4 ligand. The reported complexes are rationalized in terms of inverse coordination.

Transmission of cytomegalovirus in fresh and freeze-thawed mother's own milk to very preterm infants: a cohort study.

OBJECTIVES: The objectives of the study were to clarify: (i) the frequency of human cytomegalovirus (HCMV) transmission, (ii) the association between the viral load in mother's own milk (MOM), the amount of fresh MOM and transmission, and (iii) the frequency of sepsis-like-symptoms (SLS) among infants born to seropositive mothers compared to infants born to seronegative mothers. STUDY DESIGN: This prospective cohort study enrolled very preterm infants (gestational age <32 weeks) from Denmark. Weekly samples of fresh MOM and urine were analyzed for HCMV-DNA. RESULTS: Twenty-six very preterm infants were enrolled. Four acquired an HCMV infection, of which two developed SLS. HCMV-infected infants received MOM with a significant higher viral load compared to the HCMV-uninfected infants. CONCLUSION: A combination of a high viral load and an increased amount of fresh MOM increased the risk of HCMV transmission. SLS was only slightly more common among infants exposed to HCMV positive MOM.

E4 Transfer (E=P, As) to Ni Complexes.

The use of [Cp''2 Zr(η1:1 -E4 )] (E=P (1 a), As (1 b), Cp''=1,3-di-tert-butyl-cyclopentadienyl) as phosphorus or arsenic source, respectively, gives access to novel stable polypnictogen transition metal complexes at ambient temperatures. The reaction of 1 a/1 b with [CpR NiBr]2 (CpR =CpBn (1,2,3,4,5-pentabenzyl-cyclopentadienyl), Cp''' (1,2,4-tri-tert-butyl-cyclopentadienyl)) was studied, to yield novel complexes depending on steric effects and stoichiometric ratios. Besides the transfer of the complete En unit, a degradation as well as aggregation can be observed. Thus, the prismane derivatives [(Cp'''Ni)2 (µ,η3:3 -E4 )] (2 a (E=P); 2 b (E=As)) or the arsenic containing cubane [(Cp'''Ni)3 (µ3 -As)(As4 )] (5) are formed. Furthermore, the bromine bridged cubanes of the type [(CpR Ni)3 {Ni(µ-Br)}(µ3 -E)4 ]2 (CpR =Cp''': 6 a (E=P), 6 b (E=As), CpR =CpBn : 8 a (E=P), 8 b (E=As)) can be isolated. Here, a stepwise transfer of En units is possible, with a cyclo-E4 2- ligand being introduced and unprecedented triple-decker compounds of the type [{(CpR Ni)3 Ni(µ3 -E)4 }2 (µ,η4:4 -E'4 )] (CpR =CpBn , Cp'''; E/E'=P, As) are obtained.

Transfer Reagent for Bonding Isomers of Iron Complexes.

The cothermolysis of As4 and [Cp″2Zr(CO)2] (Cp″ = η5-C5H3tBu2) results in the formation of [Cp″2Zr(η1:1-As4)] (1) in high yields and the arsenic-rich complex [(Cp″2Zr)(Cp″Zr)(µ,η2:2:1-As5)] (2) as a minor product. In contrast to yellow arsenic, 1 is a light-stable, weighable and storable arsenic source for subsequent reactions. The transfer reaction of 1 with [Cp‴Fe(µ-Br)]2 (Cp‴ = η5-C5H2tBu3) yields the unprecedented bond isomeric complexes [(Cp‴Fe)2(µ,η4:4-As4)] (3a) and [(Cp‴Fe)2(µ,η4:4-cyclo-As4)] (3b). In contrast, the analogous reaction with the CpBn derivative [CpBnFe(µ-Br)]2 (CpBn = η5-C5(CH2(C6H5)5) leads exclusively to the triple decker complex [(CpBnFe)2(µ,η4:4-As4)] (4) possessing the tetraarsabutadiene-type ligand analogous to 3a. To elucidate the stability of the bonding isomers 3a and 3b, DFT calculations were performed. The oxidation of 4 with AgBF4 affords [(CpBnFe)2(µ,η5:5-As5)][BF4] (5), which is a product expanded by one arsenic atom, instead of the expected complex [(CpBnFe)2(µ,η4:4-cyclo-As4)]+.

Different Reactivity of As4 towards Disilenes and Silylenes.

The activation of yellow arsenic is possible with the silylene [PhC(NtBu)2 SiN(SiMe3 )2 ] (1) and the disilene [(Me3 Si)2 N(η1 -Me5 C5 )Si=Si(η1 -Me5 C5 )N(SiMe3 )2 ] (3). The reaction of As4 with 1 leads to the unprecedented As10 cage compound [(LSiN(SiMe3 )2 )3 As10 ] (2; L=PhC(NtBu)2 ) with an As7 nortricyclane core stabilized by arsasilene moieties containing silicon(II)bis(trimethylsilyl)amide substituents. In contrast, the compound [Cp*{(SiMe3 )2 N}SiAs]2 (4) containing a butterfly-like diarsadisilabicyclo[1.1.0]butane unit is formed by the reaction of As4 with the disilene 3. Both compounds were characterized by single-crystal X-ray diffraction analysis, NMR spectroscopy, and mass spectrometry. The reaction outcomes demonstrate the different reaction behavior of yellow arsenic (As4 ) compared to white phosphorus (P4 ) in the reactions with the corresponding silylenes and disilenes.

Coordination Behavior of [Cp''2 Zr(η1:1 -P4 )] towards Different Lewis Acids.

A detailed method for the preparation of [Cp''2 Zr(η1:1 -P4 )] (1) is presented. The coordination behavior of 1 towards Lewis acidic transition metal complexes of tungsten, manganese, and iron, respectively, and main group compounds (AlMe3 , AlEt3 ) was investigated in detail by computational and experimental studies. In doing so, a series of unprecedented complexes with different coordination modes and multiple coordination numbers of the tetraphosphabicyclo[1.1.0]butane framework were synthesized. All products, as well as the starting materials, were comprehensively characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and single crystal X-ray structural analysis.

Pnictogen-Silicon Analogues of Benzene.

Since the discovery of the first "inorganic benzene" (borazine, B3N3H6), the synthesis of other noncarbon derivatives is an ongoing challenge in Inorganic Chemistry. Here we report on the synthesis of the first pnictogen-silicon congeners of benzene, the triarsa- and the triphospha-trisilabenzene [(PhC(NtBu)2)3Si3E3] (E = P (1a), As (1b)) by a simple metathesis reaction. These compounds are formed by the reaction of [Cp″2Zr(η(1:1)-E4)] (E = P, As; Cp″ = C5H3tBu2) with [PhC(NtBu)2SiCl] in toluene at room temperature along with the silicon pnictogen congeners of the cyclobutadiene, [(PhC(NtBu)2)2Si2E2] (E = P (2a), As (2b)), which is unprecedented for the arsenic system 2b. All compounds were comprehensively characterized, and density functional theory calculations were performed to verify the stability and the aromatic character of the triarsa- and the triphospha-trisilabenzene.

A stable cation of a CSi3P five-membered ring with a weakly coordinating chloride anion.

Don't count on counterions: The cyclic five-membered CSi(3)P cation 1 is synthesized in the reaction of benzamidinato-stabilized chlorosilylene and methyl phosphaalkyne. The presence of four π electrons in 1 means it can be considered as a formal, heavier analogue of the cyclopentadienyl cation. Surprisingly the small counteranion (Cl(-)) does not contribute to the ring stability.

Avaliações de indicadores de cuidado de pacientes pediátricos terminais com tumores sólidos no Instituto Nacional de Câncer

Objetivo: Avaliar o cuidado de crianças com tumores sólidos incuráveis que morrem por progressão e/ou complicações terapêuticas, usando indicadores de cuidados no fim da vida. Métodos: Os dados foram coletados retrospectivamente de 207 prontuários de crianças com de tumores sólidos que morreram de 1999 a 2004, HCI- INCA. Variáveis: sexo, idade, data óbito, laudohistopatológico, estadia, número esquemas de quimioterapia, data último esquema e da última aplicação de QT, local do óbito, média de dias hospitalizados, número de episódios de hospitalização, número de consultas emergência, dias na UTI pediátrica no último mês, média de dias entre o óbito e o último esquema e última aplicação de quimioterapia. Estes dados foram utilizados para medir e comparar com os indicadores de qualidade de cuidado no fim da vida propostos por Earle et coIs para adultos portadores de neoplasias, divididos em três grupos: supertratamento no fim da vida, qualidade do planejamento do cuidado e qualidade do cuidado na morte propriamente dita. Resultados: Foram do sexo masculino: 54,6%. Os óbitos oCOrreram como conseqüência de progressão de doença em 91,8% e por complicações do tratamento em 8,2%. Locais do óbito: 88,9% foram no hospital e 8,7% foram na residência. Indicadores: 1) Indicadores de supertratamento no fim da vida: 18% fizeram quimioterapia nos últimos 14 dias (risco atribuível-RA, comparando com Earle: 0,86) e 8,7% começaram um novo esquema de QT nos últimos 30 dias (RA:3,35). A média de dias entre o último esquema de quimioterapia e a morte foi de 213,2 dias (mediana 121) e a média de dias entre a última aplicação de quimioterapia e a morte foi de 112,7 dias (mediana 43). 2.) Indicadores de Qualidade de Planejamento do Cuidado: No último mês de vida 53,6% tiveram mais de uma consulta na emergência (RA: 12,4), 23,7% tiveram mais de uma internação no hospital (RA:4,9) e a média de dias hospitalizados foi de 9,12. Foram admitidos na UTI pediátrica 23,2% (RA:4,32) e a média de dias na UTI pediátrica no último mês foi de 1,69. 3.) Indicadores de Qualidade de Cuidado na Morte propriamente dita: 100% dos pacientes não foram encaminhados a estrutura de cuidados paliativos (hospice). (RA:I,22) e 22,7% morreram na UTI pediátrica ou na emergência (RA:0,33). Conclusões: Crianças que morreram de câncer apresentaram indicadores de cuidados no fim da vida mais elevados e mais agressivos que os benchmarks prospostos por Earle para adultos com câncer. Estudos devem ser feitos para avaliar o real benefício de procedimentos terapêuticas que possam causar sofrimento as crianças no fim da vida

Purpose: To evaluate the pattern of care of children with incurable solid tumors that die of progressive disease and/or therapeutic complications, applying end of life care indicators proposed by Earle et cols for adults with malignant diseases. Casuistics and Methods: Data were retrospectively collected from 207 charts of children with solid tumors that died between 1999 and 2004, HCI- INCA. Variables: sex, age, date of death, histopathological diagnosis, stage, number of chemotherapy treatments, last schedule and last chemotherapy application date, place of death, mean hospitalization days, number of hospitalization episodes, number of emergency consultations, pediatric intensive care unit (PICU) days in the last month, mean days interval between last cycle and application of chemotherapy and death. These data were utilized to measure and to compare with indicators of quality of end of life care classified into three groups: End of life overtreatment, quality of care planning and quality of death care. Results: Male: 54.6%. Death due to disease progression: 91.8% and to treatment complications: 8,2%. Place of death: 88.9% in the hospital and 8.7% at home. 1) End of Life overtreatment Indicators: 18% received chemotherapy during the last 14 days (Attributable Risk-AR compared with Earle: 0.86) and 8.7% started a new chemotherapy schedule in the last 30 days (AR: 3.35). Mean days between the last chemotherapy schedule and death: 213.2 days (median 121) and the last chemotherapy application and death: 112.7 days (median 43); 2) Quality of care planning indicators: In the last month of life, 53.6% had more than one emergency visit (AR: 12.4) and 23.7%, more than one hospital admission (AR: 4.9), and mean hospitalization days was 9.12. Last month admission to the ICU: 23.2% (AR: 4.32) and last month mean days in the PICU: 1.69; 3) Quality of death care indicators: Patients had not been referred systematically to palliative care structure(Hospice) (AR: 1.22) e 22.7% died in the PICU or emergency room (AR: 0.33). Conclusion: Children who died of cancer, received more aggressive treatment when compared to indicators suggested by Earle et cols for adults with cancer. Studies should be performed to evaluate the real benefit of therapeutic procedures that can bring suffering to children in the last month of life

O diagnóstico tardio de rabdomiossarcoma / Late diagnosis of pediatric rhabdomyosarcoma

Objetivo: avaliar o período de tempo decorrido desde o início da sintomatologia até o diagnóstico de rabdomiossarcoma em crianças e a possível implicação na evolução e prognóstico...

Objective: to evaluate the period lenght since the beginning of symptoms until the rhabidomyosarcoma in a reference study was conducted with 163 patients aged under 16-years-old admited for treatment...