Operational research as a mechanism to improve treatment outcomes for drug-resistant TB in the WHO European Region.

In 2022, the WHO European Region accounted for 15.1% of all incident rifampicin-resistant/multidrug-resistant TB (RR/MDR-TB) cases. Most occurred in 18 high-priority countries of eastern Europe and central Asia, many of which joined an initiative led by the WHO Regional Office for Europe. The aim was to introduce three, fully oral, 9-month modified shorter treatment regimens (mSTR) to treat RR/MDR-TB under operational research conditions. The three regimens were: 1) bedaquiline + linezolid + levofloxacin + clofazimine + cycloserine (BdqLzdLfxCfzCs); 2) BdqLzdLfxCfz + delamanid (Dlm) for children over 6 years of age and adults; and 3) DlmLzdLfxCfz for children under 6 years of age. The project aimed to enhance treatment success, facilitate mSTR implementation, promote quality of care and build research capacity, while also contributing to global knowledge on all-oral mSTR use. Between April 2020 and June 2022, >2,800 patients underwent mSTR treatment in the WHO European Region. This unique experience promoted further collaboration with national tuberculosis programmes, health authorities, experts and donors within and outside Europe, with a focus on implementing operational research and improving the quality of care in high TB burden countries of the region. In the hope of encouraging others to adopt this model, we have described the principles of the initiative, its strengths and weaknesses and next steps.

En 2022, la Région européenne de l'OMS a recensé 15,1% de l'ensemble des cas de TB résistante à la rifampicine/multirésistante aux médicaments (RR/MDR-TB). La majorité de ces cas ont eu lieu dans 18 pays hautement prioritaires d'Europe orientale et d'Asie centrale, parmi lesquels de nombreux ont adhéré à une initiative dirigée par le Bureau régional de l'OMS pour l'Europe. L'objectif était de mettre en place trois schémas thérapeutiques modifiés plus courts de 9 mois, entièrement oraux, (mSTR, pour l'anglais "fully oral, 9-month modified shorter treatment regimens ¼) pour le traitement de la RR/MDR-TB dans le cadre d'une recherche opérationnelle. Ces trois schémas étaient les suivants 1) bédaquiline + linézolide + lévofloxacine + clofazimine + cyclosérine (BdqLzdLfxCfzCs) ; 2) BdqLzdLfxCfz + delamanid (Dlm) pour les enfants de plus de 6 ans et les adultes ; et 3) DlmLzdLfxCfz pour les enfants de moins de 6 ans. Le projet visait à améliorer l'efficacité des traitements, à faciliter l'application des mSTR, à promouvoir la qualité des soins et à renforcer les capacités de recherche, tout en contribuant aux connaissances mondiales sur l'utilisation des mSTR par voie orale. Entre avril 2020 et juin 2022, plus de 2 800 patients ont reçu un traitement par mSTR dans la Région Européenne de l'OMS. Cette expérience unique a encouragé la continuation de la collaboration avec les programmes nationaux de lutte contre la TB, les autorités sanitaires, les experts et les donateurs tant en Europe qu'à l'étranger. L'accent est mis sur la mise en œuvre de la recherche opérationnelle et l'amélioration de la qualité des soins dans les pays de la région où la TB est fortement prévalente. Nous avons détaillé les principes de l'initiative, ses avantages et ses inconvénients, dans l'espoir d'inciter d'autres pays à suivre cet exemple, tout en exposant les étapes à venir.

TB and poverty: the effect of rifampicin-resistant TB on household income.

SETTING: The Republic of Moldova, one of Europe's poorest countries, also bears one of the highest burdens of rifampicin-resistant TB (RR-TB). OBJECTIVES: To trace the patients' journey through TB in terms of the relationship with poverty and assess its determinants. DESIGN: This cross-sectional study used secondary data from a survey assessing catastrophic costs in RR-TB-affected households. RESULTS: Data were obtained from 430 RR-TB patients. The percentage of poor TB-affected households rose from 65% prior to TB to 86% after TB treatment completion (P < 0.001). Social factors leading to poverty were identified for each stage: diagnostic period (history of incarceration: cOR 2.3, 95% CI 1.1-5.2); treatment period (being unemployed or unofficially employed: cOR 6.7, 95% CI 4.3-10.0); and post-treatment (being married or cohabiting: cOR 5.7, 95% CI 2.9-11.0). Participants who had ≥3 members in their households were more likely to be poor at all TB stages: diagnostic period (cOR 5.7, 95% CI 3.7-8.8), treatment period (cOR 3.8, 95% CI 2.5-5.6) and post-treatment (cOR 7.2, 95% CI 3.6-14.3). CONCLUSION: The study identified risk factors associated with poverty at each stage of TB. These findings outline that innovative social protection policies are required to protect TB patients against poverty.

CONTEXTE: La République de Moldavie est l'un des pays les plus pauvres d'Europe et l'un des plus touchés par la TB résistante à la rifampicine (RR-TB). OBJECTIFS: Nous avons cartographié le parcours des patients atteints de TB en lien avec la pauvreté et évalué les déterminants associés. MÉTHODE: Cette étude transversale a analysé des données secondaires issues d'une enquête évaluant les coûts catastrophiques supportés par les ménages touchés par la RR-TB. RÉSULTATS: Des données ont été recueillies auprès de 430 patients atteints de RR-TB. Le taux de ménages pauvres touchés par la TB est passé de 65% avant le traitement à 86% après la fin du traitement de la TB (P < 0,001). Pour chaque stade de la TB, les facteurs sociaux conduisant à la pauvreté ont été identifiés : période de diagnostic (antécédents d'emprisonnement : rapport de cotes brut (cOR) 2,3, IC à 95% 1,1­5,2) ; période de traitement (être au chômage ou employé officieux : cOR 6,7 ; IC 95% 4,3­10,0) ; et post-traitement (être marié ou cohabitant : cOR 5,7, IC 95% 2,9­11,0). Les participants dont le ménage comptait ≥3 membres étaient plus susceptibles d'être pauvres à tous les stades de la TB : période de diagnostic (cOR 5,7 ; IC à 95% 3,7­8,8), période de traitement (cOR 3,8 ; IC à 95% 2,5­5,6) et post-traitement (cOR 7,2 ; IC à 95% 3,6­14,3). CONCLUSION: L'étude a permis d'identifier des facteurs de risque liés à la pauvreté à toutes les étapes de la TB. Ces résultats soulignent l'importance de mettre en place des politiques de protection sociale novatrices pour prévenir l'appauvrissement des patients atteints de TB.

Point Absorber Limits to Future Gravitational-Wave Detectors.

High-quality optical resonant cavities require low optical loss, typically on the scale of parts per million. However, unintended micron-scale contaminants on the resonator mirrors that absorb the light circulating in the cavity can deform the surface thermoelastically and thus increase losses by scattering light out of the resonant mode. The point absorber effect is a limiting factor in some high-power cavity experiments, for example, the Advanced LIGO gravitational-wave detector. In this Letter, we present a general approach to the point absorber effect from first principles and simulate its contribution to the increased scattering. The achievable circulating power in current and future gravitational-wave detectors is calculated statistically given different point absorber configurations. Our formulation is further confirmed experimentally in comparison with the scattered power in the arm cavity of Advanced LIGO measured by in situ photodiodes. The understanding presented here provides an important tool in the global effort to design future gravitational-wave detectors that support high optical power and thus reduce quantum noise.

Modeling circulating cavity fields using the discrete linear canonical transform.

Fabry-Perot cavities are central to many optical measurement systems. In high-precision experiments, such as aLIGO and AdVirgo, coupled cavities are often required, leading to complex optical behavior. We show, for the first time to our knowledge, that discrete linear canonical transforms (LCTs) can be used to compute circulating optical fields for cavities in which the optics have arbitrary apertures, reflectance and transmittance profiles, and shape. We compare the predictions of LCT models with those of alternative methods. To further highlight the utility of the LCT, we present a case study of point absorbers on the aLIGO mirrors and compare it with recently published results.

Mode matching error signals using radio-frequency beam shape modulation.

Precise mode matching is needed to maximize performance in coupled cavity interferometers such as Advanced Laser Interferometer Gravitational-Wave Observatory (LIGO). In this paper, we present a new mode matching sensing scheme, to the best of our knowledge, that uses a single radio-frequency higher-order-mode sideband and single-element photodiodes. It is first-order insensitive to misalignment and can serve as an error signal in a closed loop control system for a set of mode matching actuators. We also discuss how it may be implemented in Advanced LIGO. The proposed mode matching error signal has been successfully demonstrated on a tabletop experiment, where the error signal increased the mode matching of a beam to a cavity to 99.9%.

Iatrogenic Cushing's syndrome as a consequence of nasal use of Betamethasone spray during pregnancy.

INTRODUCTION: Glucocorticoids (GC) are largely used for their anti-inflammatory and immunosuppressive effects. Until recently "local" administration (inhalation, topical, intra-articular, ocular and nasal) was considered devoid of important systemic side effects, but there is no administration form, dosing or treatment duration for which the risk of iatrogenic Cushing's syndrome (CS) and consequent adrenal insufficiency (AI) can be excluded with certainty. PATIENTS AND METHODS: We present the case of a pregnant woman who developed overt CS with secondary AI in the second trimester of pregnancy. She had low morning plasma cortisol 6.95 nmol/L (normal non-pregnant range 166 - 507) and low ACTH level 1.54 pg/mL (normal range 7.2 - 63.3), suggestive for iatrogenic CS. A thorough anamnesis revealed chronic sinusitis long-term treated with high doses of intranasal betamethasone spray (6 - 10 applications/day, approximately 10 mg betamethasone/week, for 5 months). After decreasing the dose and switching to an alpha-1 adrenergic agonist spray, the adrenal function recovered in a few weeks without manifestations of AI. The patient underwent an uneventful delivery of a normal baby. A review of the literature showed that only a few cases with exogenous CS and consequent AI caused by intranasal GC administration were described, mostly in children, but none during pregnancy. CONCLUSION: Long-term high doses of intranasal GC may induce iatrogenic CS and should be avoided. Low levels of ACTH and cortisol should prompt a detailed anamnesis looking for various types of glucocorticoid administration.

Value of routine ultrasound examination at 35-37 weeks' gestation in diagnosis of non-cephalic presentation.

OBJECTIVE: Undiagnosed non-cephalic presentation in labor carries increased risks for both the mother and baby. Routine pregnancy care based on maternal abdominal palpation fails to detect the majority of cases of non-cephalic presentation. The aim of this study was to report the incidence of non-cephalic presentation at a routine scan at 35 + 0 to 36 + 6 weeks' gestation and the subsequent management of such pregnancies. METHODS: This was a retrospective analysis of prospectively collected data in 45 847 singleton pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Patients with breech or transverse/oblique presentation were divided into two groups; first, those who would have elective Cesarean section for fetal or maternal indications other than the abnormal presentation, and, second, those who would potentially require external cephalic version (ECV). The latter group was reassessed after 1-2 weeks and, if there was persistence of abnormal presentation, the parents were offered the option of ECV or elective Cesarean section at 38-40 weeks' gestation. Multivariable logistic regression analysis was carried out to determine which of the factors from maternal and pregnancy characteristics provided a significant contribution in the prediction of, first, non-cephalic presentation at the 35 + 0 to 36 + 6-week scan, second, successful ECV from non-cephalic to cephalic presentation, and, third, spontaneous rotation from non-cephalic to cephalic presentation that persisted until delivery. RESULTS: First, at 35 + 0 to 36 + 6 weeks, the fetal presentation was cephalic in 43 416 (94.7%) pregnancies, breech in 1987 (4.3%) and transverse or oblique in 444 (1.0%). Second, multivariable analysis demonstrated that the risk of non-cephalic presentation increased with increasing maternal age and weight, decreasing height and earlier gestational age at scan, was higher in the presence of placenta previa, oligohydramnios or polyhydramnios and in nulliparous than parous women, and was lower in women of South Asian or mixed racial origin than in white women. Third, 22% of cases of non-cephalic presentation were not eligible for ECV because of planned Cesarean section for indications other than the malpresentation. Fourth, of those eligible for ECV, only 48.5% (646/1332) agreed to the procedure, which was successful in 39.0% (252/646) of cases. Fifth, the chance of successful ECV increased with increasing maternal age and was lower in nulliparous than parous women. Sixth, in 33.9% (738/2179) of pregnancies with non-cephalic presentation in which successful ECV was not carried out, there was subsequent spontaneous rotation to cephalic presentation. Seventh, the chance of spontaneous rotation from non-cephalic to cephalic presentation increased with increasing interval between the scan and delivery, decreased with increasing birth-weight percentile, was higher in women of black than those of white racial origin, if presentation was transverse or oblique rather than breech and if there was polyhydramnios, and was lower in nulliparous than parous women and in the presence of placenta previa. Eighth, in 109 (0.3%) cephalic presentations, there was subsequent rotation to non-cephalic presentation and, in 41% of these, the diagnosis was made during labor. Ninth, of the total 2431 cases of non-cephalic presentation at the time of the scan, presentation at birth was cephalic in 985 (40.5%); in 738 (74.9%) this was due to spontaneous rotation and in 247 (25.1%) this was due to successful ECV. Tenth, prediction of non-cephalic presentation at the 35 + 0 to 36 + 6-week scan and successful ECV from maternal and pregnancy factors was poor, but prediction of spontaneous rotation from non-cephalic to cephalic presentation that persisted until delivery was moderately good and this could be incorporated in the counseling of women prior to ECV. CONCLUSIONS: The problem of unexpected non-cephalic presentation in labor can, to a great extent, be overcome by a routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. The incidence of non-cephalic presentation at the 35 + 0 to 36 + 6-week scan was about 5%, but, in about 40% of these cases, the presentation at birth was cephalic, mainly due to subsequent spontaneous rotation and, to a lesser extent, as a consequence of successful ECV. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Two-stage approach for prediction of small-for-gestational-age neonate and adverse perinatal outcome by routine ultrasound examination at 35-37 weeks' gestation.

BACKGROUND: Justification of prenatal screening for small-for-gestational-age (SGA) fetuses near term is based on, first, evidence that such fetuses/neonates are at increased risk of stillbirth and adverse perinatal outcome, and, second, the expectation that these risks can be reduced by medical interventions, such as early delivery. However, there are no randomized studies demonstrating that routine screening for SGA fetuses and appropriate interventions in the high-risk group can reduce adverse perinatal outcome. Before such meaningful studies can be undertaken, it is essential that the best approach for effective identification of SGA neonates is determined, and that the contribution of SGA neonates to the overall rate of adverse perinatal outcome is established. In a previous study of pregnancies undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation, we found that, first, screening by estimated fetal weight (EFW) < 10th percentile provided poor prediction of SGA neonates and, second, prediction of > 85% of SGA neonates requires use of EFW < 40th percentile. OBJECTIVES: To examine the contribution of SGA fetuses to the overall rate of adverse perinatal outcome and, to propose a two-stage approach for prediction of a SGA neonate at routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. METHODS: This was a prospective study of 45 847 singleton pregnancies undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. First, we examined the relationship between birth-weight percentile and adverse perinatal outcome, defined as stillbirth, neonatal death or admission to the neonatal unit for ≥ 48 h. Second, we used a two-stage approach for prediction of a SGA neonate and adverse perinatal outcome; in the first stage, fetal biometry was used to distinguish between pregnancies at very low risk (EFW ≥ 40th percentile) and those at increased risk (EFW < 40th percentile) and, in the second stage, the pregnancies with EFW < 40th percentile were stratified into high-, intermediate- and low-risk groups based on the results of EFW and pulsatility index in the uterine arteries, umbilical artery and fetal middle cerebral artery. Different percentiles of EFW and Doppler indices were used to define each risk category, and the performance of screening for a SGA neonate and adverse perinatal outcome in pregnancies delivered at ≤ 2, 2.1-4 and > 4 weeks after assessment was determined. We propose that the high-risk group would require monitoring from initial assessment to delivery, the intermediate-risk group would require monitoring from 2 weeks after initial assessment to delivery, the low-risk group would require monitoring from 4 weeks after initial assessment to delivery, and the very low-risk group would not require any further reassessment. RESULTS: First, although in neonates with low birth weight (< 10th percentile) the risk of adverse perinatal outcome is increased, 84% of adverse perinatal events occur in the group with birth weight ≥ 10th percentile. Second, in screening by EFW < 10th percentile, the predictive performance for a SGA neonate is modest for those born at ≤ 2 weeks after assessment (83% and 69% for neonates with birth weight < 3rd and < 10th percentiles, respectively), but poor for those born at 2.1-4 weeks (65% and 45%, respectively) and > 4 weeks (40% and 30%, respectively) after assessment. Third, improved performance of screening, especially for those delivered at > 2 weeks after assessment, is potentially achieved by a proposed new approach for stratifying pregnancies into management groups based on findings of EFW and Doppler indices (prediction of birth weight < 3rd and < 10th percentiles for deliveries at ≤ 2, 2.1-4 and > 4 weeks after assessment: 89% and 75%, 83% and 74%, and 88% and 82%, respectively). Fourth, the predictive performance for adverse perinatal outcome of EFW < 10th percentile is very poor (26%, 9% and 5% for deliveries at ≤ 2, 2.1-4 and > 4 weeks after assessment, respectively) and this is improved by the proposed new approach (31%, 22% and 29%, respectively). CONCLUSIONS: This study presents an approach for stratifying pregnancies undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation into four management groups based on findings of EFW and Doppler indices. This approach potentially has a higher predictive performance for a SGA neonate and adverse perinatal outcome than that of screening by EFW < 10th percentile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of large-for-gestational-age neonate by routine third-trimester ultrasound.

OBJECTIVES: First, to evaluate and compare the performance of routine ultrasonographic estimated fetal weight (EFW) and fetal abdominal circumference (AC) at 31 + 0 to 33 + 6 and 35 + 0 to 36 + 6 weeks' gestation in the prediction of a large-for-gestational-age (LGA) neonate born at ≥ 37 weeks' gestation. Second, to assess the additive value of fetal growth velocity between 32 and 36 weeks' gestation to the performance of EFW at 35 + 0 to 36 + 6 weeks' gestation for prediction of a LGA neonate. Third, to define the predictive performance for a LGA neonate of different EFW cut-offs on routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Fourth, to propose a two-stage strategy for identifying pregnancies with a LGA fetus that may benefit from iatrogenic delivery during the 38th gestational week. METHODS: This was a retrospective study. First, data from 21 989 singleton pregnancies that had undergone routine ultrasound examination at 31 + 0 to 33 + 6 weeks' gestation and 45 847 that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks were used to compare the predictive performance of EFW and AC for a LGA neonate with birth weight > 90th and > 97th percentiles born at ≥ 37 weeks' gestation. Second, data from 14 497 singleton pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation and had a previous scan at 30 + 0 to 34 + 6 weeks were used to determine, through multivariable logistic regression analysis, whether addition of growth velocity, defined as the difference in EFW Z-score or AC Z-score between the early and late third-trimester scans divided by the time interval between the scans, improved the performance of EFW at 35 + 0 to 36 + 6 weeks in the prediction of delivery of a LGA neonate at ≥ 37 weeks' gestation. Third, in the database of the 45 847 pregnancies that had undergone routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation, the screen-positive and detection rates for a LGA neonate born at ≥ 37 weeks' gestation and ≤ 10 days after the initial scan were calculated for different EFW percentile cut-offs between the 50th and 90th percentiles. RESULTS: First, the areas under the receiver-operating characteristics curves (AUC) of screening for a LGA neonate were significantly higher using EFW Z-score than AC Z-score and at 35 + 0 to 36 + 6 than at 31 + 0 to 33 + 6 weeks' gestation (P < 0.001 for all). Second, the performance of screening for a LGA neonate achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks was not significantly improved by addition of EFW growth velocity or AC growth velocity. Third, in screening by EFW > 90th percentile at 35 + 0 to 36 + 6 weeks' gestation, the predictive performance for a LGA neonate born at ≥ 37 weeks' gestation was modest (65% and 46% for neonates with birth weight > 97th and > 90th percentiles, respectively, at a screen-positive rate of 10%), but the performance was better for prediction of a LGA neonate born ≤ 10 days after the scan (84% and 71% for neonates with birth weight > 97th and > 90th percentiles, respectively, at a screen-positive rate of 11%). Fourth, screening by EFW > 70th percentile at 35 + 0 to 36 + 6 weeks' gestation predicted 91% and 82% of LGA neonates with birth weight > 97th and > 90th percentiles, respectively, born at ≥ 37 weeks' gestation, at a screen-positive rate of 32%, and the respective values of screening by EFW > 85th percentile for prediction of a LGA neonate born ≤ 10 days after the scan were 88%, 81% and 15%. On the basis of these results, it was proposed that routine fetal biometry at 36 weeks' gestation is a screening rather than diagnostic test for fetal macrosomia and that EFW > 70th percentile should be used to identify pregnancies in need of another scan at 38 weeks, at which those with EFW > 85th percentile should be considered for iatrogenic delivery during the 38th week. CONCLUSIONS: First, the predictive performance for a LGA neonate by routine ultrasonographic examination during the third trimester is higher if the scan is carried out at 36 than at 32 weeks, the method of screening is EFW than fetal AC, the outcome measure is birth weight > 97th than > 90th percentile and if delivery occurs within 10 days than at any stage after assessment. Second, prediction of a LGA neonate by EFW > 90th percentile is modest and this study presents a two-stage strategy for maximizing the prenatal prediction of a LGA neonate. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Routine ultrasound at 32 vs 36 weeks' gestation: prediction of small-for-gestational-age neonates.

OBJECTIVE: To evaluate and compare the performance of routine ultrasonographic estimated fetal weight (EFW) and fetal abdominal circumference (AC) at 31 + 0 to 33 + 6 and 35 + 0 to 36 + 6 weeks' gestation in the prediction of a small-for-gestational-age (SGA) neonate. METHODS: This was a prospective study of 21 989 singleton pregnancies undergoing routine ultrasound examination at 31 + 0 to 33 + 6 weeks' gestation and 45 847 undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. In each case, the estimated fetal weight (EFW) from measurements of fetal head circumference, AC and femur length was calculated using the Hadlock formula and expressed as a percentile according to The Fetal Medicine Foundation fetal and neonatal population weight charts. The same charts were used for defining a SGA neonate with birth weight < 10th and < 3rd percentiles. For each gestational-age window, the screen-positive and detection rates, at different EFW percentile cut-offs between the 10th and 50th percentiles, were calculated for prediction of delivery of a SGA neonate with birth weight < 10th and < 3rd percentiles within 2 weeks and at any stage after assessment. The areas under the receiver-operating characteristics curves (AUC) in screening for a SGA neonate by EFW and AC at 31 + 0 to 33 + 6 and at 35 + 0 to 36 + 6 weeks' gestation were compared. RESULTS: First, the AUCs in screening by EFW for a SGA neonate with birth weight < 10th and < 3rd percentiles delivered within 2 weeks and at any stage after screening at 35 + 0 to 36 + 6 weeks' gestation were significantly higher than those at 31 + 0 to 33 + 6 weeks (P < 0.001). Second, at both 35 + 0 to 36 + 6 and 31 + 0 to 33 + 6 weeks' gestation, the predictive performance for a SGA neonate with birth weight < 10th and < 3rd percentiles born at any stage after screening was significantly higher using EFW Z-score than AC Z-score. Similarly, at 35 + 0 to 36 + 6 weeks, but not at 31 + 0 to 33 + 6 weeks, the predictive performance for a SGA neonate with birth weight < 10th and < 3rd percentiles born within 2 weeks after screening was significantly higher using EFW Z-score than AC Z-score. Third, screening by EFW < 10th percentile at 35 + 0 to 36 + 6 weeks' gestation predicted 70% and 84% of neonates with birth weight < 10th and < 3rd percentiles, respectively, born within 2 weeks after assessment, and the respective values for a neonate born at any stage after assessment were 46% and 65%. Fourth, prediction of > 85% of SGA neonates with birth weight < 10th percentile born at any stage after screening at 35 + 0 to 36 + 6 weeks' gestation requires use of EFW < 40th percentile. Screening at this percentile cut-off predicted 95% and 99% of neonates with birth weight < 10th and < 3rd percentiles, respectively, born within 2 weeks after assessment, and the respective values for a neonate born at any stage after assessment were 87% and 94%. CONCLUSIONS: The predictive performance for a SGA neonate of routine ultrasonographic examination during the third trimester is higher if, first, the scan is carried out at 35 + 0 to 36 + 6 weeks' gestation than at 31 + 0 to 33 + 6 weeks, second, the method of screening is EFW than fetal AC, third, the outcome measure is birth weight < 3rd than < 10th percentile, and, fourth, if delivery occurs within 2 weeks than at any stage after assessment. Prediction of a SGA neonate by EFW < 10th percentile is modest and prediction of > 85% of cases at 35 + 0 to 36 + 6 weeks' gestation necessitates use of EFW < 40th percentile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 32 and 36 weeks.

OBJECTIVE: To assess the additive value of fetal growth velocity between 32 and 36 weeks' gestation to the performance of ultrasonographic estimated fetal weight (EFW) at 35 + 0 to 36 + 6 weeks' gestation for prediction of delivery of a small-for-gestational-age (SGA) neonate and adverse perinatal outcome. METHODS: This was a prospective study of 14 497 singleton pregnancies undergoing routine ultrasound examination at 30 + 0 to 34 + 6 and at 35 + 0 to 36 + 6 weeks' gestation. Multivariable logistic regression analysis was used to determine whether addition of growth velocity, defined as the difference in EFW Z-score or abdominal circumference (AC) Z-score between the early and late third-trimester scans divided by the time interval between the scans, improved the performance of EFW Z-score at 35 + 0 to 36 + 6 weeks in the prediction of, first, delivery of a SGA neonate with birth weight < 10th and < 3rd percentiles within 2 weeks and at any stage after assessment and, second, a composite of adverse perinatal outcome, defined as stillbirth, neonatal death or admission to the neonatal unit for ≥ 48 h. RESULTS: Multivariable logistic regression analysis demonstrated that significant contributors to the prediction of a SGA neonate were EFW Z-score at 35 + 0 to 36 + 6 weeks' gestation, fetal growth velocity, by either AC Z-score or EFW Z-score, and maternal risk factors. The area under the receiver-operating characteristics curve (AUC) and detection rate (DR), at a 10% screen-positive rate, for prediction of a SGA neonate < 10th percentile born within 2 weeks after assessment achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks (AUC, 0.938 (95% CI, 0.928-0.947); DR, 80.7% (95% CI, 77.6-83.9%)) were not significantly improved by addition of EFW growth velocity and maternal risk factors (AUC, 0.941 (95% CI, 0.932-0.950); P = 0.061; DR, 82.5% (95% CI, 79.4-85.3%)). Similar results were obtained when growth velocity was defined by AC rather than EFW. Similarly, there was no significant improvement in the AUC and DR, at a 10% screen-positive rate, for prediction of a SGA neonate < 10th percentile born at any stage after assessment or a SGA neonate < 3rd percentile born within 2 weeks or at any stage after assessment, achieved by EFW Z-score at 35 + 0 to 36 + 6 weeks by addition of maternal factors and either EFW growth velocity or AC growth velocity. Multivariable logistic regression analysis demonstrated that the only significant contributor to adverse perinatal outcome was maternal risk factors. Multivariable logistic regression analysis in the group with EFW < 10th percentile demonstrated that significant contribution to prediction of delivery of a neonate with birth weight < 10th and < 3rd percentiles and adverse perinatal outcome was provided by EFW Z-score at 35 + 0 to 36 + 6 weeks, but not by AC growth velocity < 1st decile. CONCLUSION: The predictive performance of EFW at 35 + 0 to 36 + 6 weeks' gestation for delivery of a SGA neonate and adverse perinatal outcome is not improved by addition of estimated growth velocity between 32 and 36 weeks' gestation. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of small-for-gestational-age neonates at 35-37 weeks' gestation: contribution of maternal factors and growth velocity between 20 and 36 weeks.

OBJECTIVES: To evaluate the performance of ultrasonographic estimated fetal weight (EFW) at 35 + 0 to 36 + 6 weeks' gestation in the prediction of delivery of a small-for-gestational-age (SGA) neonate and assess the additive value of, first, maternal risk factors and, second, fetal growth velocity between 20 and 36 weeks' gestation in improving such prediction. METHODS: This was a prospective study of 44 043 singleton pregnancies undergoing routine ultrasound examination at 19 + 0 to 23 + 6 and at 35 + 0 to 36 + 6 weeks' gestation. Multivariable logistic regression analysis was used to determine whether addition of maternal risk factors and growth velocity, the latter defined as the difference in EFW Z-score or fetal abdominal circumference (AC) Z-score between the third- and second-trimester scans divided by the time interval between the scans, improved the performance of EFW Z-score at 35 + 0 to 36 + 6 weeks in the prediction of delivery of a SGA neonate with birth weight < 10th and < 3rd percentiles within 2 weeks and at any stage after assessment. RESULTS: Screening by EFW Z-score at 35 + 0 to 36 + 6 weeks' gestation predicted 63.4% (95% CI, 62.0-64.7%) of neonates with birth weight < 10th percentile and 74.2% (95% CI, 72.2-76.1%) of neonates with birth weight < 3rd percentile born at any stage after assessment, at a screen-positive rate of 10%. The respective values for SGA neonates born within 2 weeks after assessment were 76.8% (95% CI, 74.4-79.0%) and 81.3% (95% CI, 78.2-84.0%). For a desired 90% detection rate of SGA neonate delivered at any stage after assessment, the necessary screen-positive rate would be 33.7% for SGA < 10th percentile and 24.4% for SGA < 3rd percentile. Multivariable logistic regression analysis demonstrated that, in the prediction of a SGA neonate with birth weight < 10th and < 3rd percentiles, there was a significant contribution from EFW Z-score at 35 + 0 to 36 + 6 weeks' gestation, maternal risk factors and AC growth velocity, but not EFW growth velocity. However, the area under the receiver-operating characteristics curve for prediction of delivery of a SGA neonate by screening with maternal risk factors and EFW Z-score was not improved by addition of AC growth velocity. CONCLUSION: Screening for SGA neonates by EFW at 35 + 0 to 36 + 6 weeks' gestation and use of the 10th percentile as the cut-off predicts 63% of affected neonates. Prediction of 90% of SGA neonates necessitates classification of about 35% of the population as being screen positive. The predictive performance of EFW is not improved by addition of estimated growth velocity between the second and third trimesters of pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Fetal Medicine Foundation reference ranges for umbilical artery and middle cerebral artery pulsatility index and cerebroplacental ratio.

OBJECTIVES: To develop gestational age-based reference ranges for the pulsatility index in the umbilical artery (UA-PI) and fetal middle cerebral artery (MCA-PI) and the cerebroplacental ratio (MCA-PI/UA-PI), and to examine the maternal characteristics and medical history that affect these measurements. METHODS: This was a cross-sectional study of 72 387 pregnancies undergoing routine ultrasound examination at 20 + 0 to 22 + 6 weeks' gestation (n = 3712), 31 + 0 to 33 + 6 weeks (n = 29 035), 35 + 0 to 36 + 6 weeks (n = 37 252) or 41 + 0 to 41 + 6 weeks (n = 2388). For the purpose of this study, we included data for only one of the second- or third-trimester visits. The inclusion criteria were singleton pregnancy, dating by fetal crown-rump length at 11 + 0 to 13 + 6 weeks' gestation, live birth of a morphologically normal neonate and ultrasonographic measurements by sonographers who had received the Fetal Medicine Foundation Certificate of Competence in Doppler ultrasound. Since the objectives of the study were to establish reference ranges, rather than normal ranges, and to examine factors from maternal characteristics and medical history that affect these measurements, we included all pregnancies having routine ultrasound examinations, irrespective of whether the mother had a pre-existing medical condition, such as diabetes mellitus, or a pregnancy complication, such as pre-eclampsia or suspected fetal growth restriction. Median and SD models were fitted between UA-PI, MCA-PI and CPR and gestational age. Assessment of goodness of fit of the models was by inspection of quantile-to-quantile (Q-Q) plots of Z-scores calculated using the mean and SD models. The distributions of MCA-PI, UA-PI and CPR Z-scores were examined in relation to maternal characteristics and medical history. RESULTS: The relationship between the median and gestational age was linear for UA-PI and cubic for MCA-PI and CPR and the SD was log quadratic for all three. MCA-PI and CPR increased with gestational age from 20 weeks' gestation to reach a peak at around 32 and 34 weeks, respectively, and decreased thereafter, whereas UA-PI decreased linearly with gestational age from 20 to 42 weeks. Compared to the general population, significant deviations in multiples of the median values of UA-PI, MCA-PI and CPR were observed in subgroups of maternal age, body mass index, racial origin, method of conception and parity. CONCLUSION: This study established new reference ranges for UA-PI, MCA-PI and CPR, according to gestational age, and reports maternal characteristics and medical history that affect these measurements. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Научное обоснование поправок в закон о контроле над алкоголем, направленных на сокращение вредного потребления алкоголя в Республике Молдова: Аналитический обзор EVIPNet для формирования политики, номер 4

В Республике Молдова алкоголь находится в свободном доступе для населения, даже для детей,что приводит к высокому уровню потребления и тяжелым последствиям, обусловленнымалкоголем, для здоровья и экономики как среди населения, так и в обществе в целом. Этупроблему усугубляет неполнота, неадекватность и ненадлежащее применение нормативныхактов, связанных с политикой ценообразования на алкоголь и запретами на рекламу, а такженеограниченный доступ к пиву, вину и винодельческой продукции в розничной торговле. ВОЗ призвала все государства-члены (включая Республику Молдова) принять мерыдля устранения вреда, связанного с алкоголем, обратившись с просьбой о проведенииэффективных мероприятий по снижению вреда. В Европе в период 2006-2010 гг. резкорасширились просветительская и общественная деятельность в отношении политики контролянад алкоголем; однако политика в области ценообразования и контроля над рекламой ослабла,и, согласно анализу, проведенному Центром наркологии и психического здоровья, это был«просто неверный подход». Некоторые научно обоснованные меры вмешательства описаны вподразделах ниже. Они доказали свою эффективность в борьбе с употреблением алкоголя идолжны стать частью национального законодательства по борьбе с алкоголем.

Informing amendments to the alcohol control legislation directed at reducing harmful use of alcohol in the Republic of Moldova: EVIPNet evidence brief for policy, number 4

In the Republic of Moldova, alcohol is readily accessible to the whole population, even children, leading to high consumption levels and a number of alcohol-related negative health and economic consequences. This problem is amplified by incomplete, inadequate and improperly implemented regulations related to policies on alcohol pricing and advertising bans, as well as unrestricted access to beer, wine and wine products in retail outlets.WHO has called upon all Member States (including the Republic of Moldova) to address alcohol-related harm by requesting implementation of effective harm-reduction interventions. In Europe in the period 2006–2010 education and community actions in the area of alcohol control policies expanded rapidly; however, the policies on pricing and advertising control grew weaker and, according to analysis carried out by the Centre for Addiction and Mental Health, this was “simply the wrong way round”. Some evidencebased interventions are outlined in the subsections below. These have proven to be effective in alcohol consumption control and should be part of national legislation on alcohol control.