Pregnancy outcomes in mothers of offspring with inherited bone marrow failure syndromes.

BACKGROUND: Children with inherited bone marrow failure syndromes (IBMFSs) may be symptomatic in utero, resulting in maternal and fetal problems during the pregnancy. Subsequent pregnancies by their mothers should be considered "high risk". METHODS: We retrospectively analyzed outcomes of 575 pregnancies in 165 unaffected mothers of offspring with Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SDS) for events noted during pregnancy, labor, and delivery. We compared outcomes of pregnancies with affected and unaffected offspring within each group of mothers and with the general population. RESULTS: The rates of miscarriage (12-20%), elective abortion (5-10%), and live birth (68-78%) among mothers of all IBMFS groups were similar and comparable with general population rates but recurrent miscarriages (≥2) were significantly more common in mothers of offspring with DBA and SDS. Offspring with FA were more frequently born small for gestational age (SGA) than unaffected babies (39% vs. 4%) and had fetal malformations (46%) with 18% having three or more, often necessitating early delivery and surgery; offspring with DC had higher rates of SGA (39% vs. 8%) and fetal distress (26% vs. 3%); and offspring with DBA had fetal hypoxia (19% vs. 1%) leading to preterm and emergency cesarean deliveries (26% vs. 6%). Offspring with early-onset severe phenotypes had the most prenatal and peripartum adverse events. CONCLUSION: We identified the high-risk nature of pregnancies in mothers with IBMFS-affected fetuses, suggesting the need for prepregnancy counseling and monitoring of subsequent pregnancies by high-risk fetal-maternal specialists.

Optimizing usability of a mobile health intervention for Spanish-speaking Latinx people with HIV through user-centered design: a post-implementation study.

Objective: Latinx people comprise 30% of all new human immunodeficiency virus (HIV) infections in the United States and face many challenges to accessing and engaging with HIV care. To bridge these gaps in care, a Spanish-language mobile health (mHealth) intervention known as ConexionesPositivas (CP) was adapted from an established English-language platform called PositiveLinks (PL) to help improve engagement in care and reduce viral nonsuppression among its users. We aimed to determine how CP can address the challenges that Latinx people with HIV (PWH) in the United States face. Materials and methods: We conducted a post-implementation study of the CP mHealth platform, guided by principles of user-centered design. We enrolled 20 Spanish-speaking CP users in the study, who completed the previously validated System Usability Scale (SUS) and semistructured interviews. Interviews were transcribed and translated for analysis. We performed thematic coding of interview transcripts in Dedoose. Results: The SUS composite score was 75, which is within the range of good usability. Four categories of themes were identified in the interviews: client context, strengths of CP, barriers to use and dislikes, and suggestions to improve CP. Positive impacts included encouraging self-monitoring of medication adherence, mood and stress, connection to professional care, and development of a support system for PWH. Discussion: While CP is an effective and easy-to-use application, participants expressed a desire for improved personalization and interactivity, which will guide further iteration. Conclusion: This study highlights the importance of tailoring mHealth interventions to improve equity of access, especially for populations with limited English proficiency.

Cancer in Noonan, Costello, cardiofaciocutaneous and LEOPARD syndromes.

Noonan syndrome (NS), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and LEOPARD syndrome (now also referred to as Noonan syndrome with multiple lentigines or NSML) are clinically overlapping dominant disorders that are caused by mutations in RAS signaling pathway genes. The spectrum of cancer susceptibility in this group of disorders has not been studied in detail. We identified more than 1900 cases of NS, CS, CFCS, or NSML reported in the literature between 1937 and 2010; 88 cancers were reported. The most common cancers reported in 1051 NS subjects were neuroblastoma (n = 8), acute lymphoblastic leukemia (n = 8), low grade glioma (n = 6), and rhabdomyosarcoma (n = 6). These associations are biologically plausible, given that somatic RAS pathway mutations are known to occur in these specific cancers. In addition, 40 childhood cases of myeloproliferative disease were described in individuals with NS, several of whom experienced a benign course of this hematologic condition. We confirmed the previously described association between CS and cancer in 268 reported individuals: 19 had rhabdomyosarcoma, 4 had bladder cancer, and 5 had neuroblastoma. By age 20, the cumulative incidence of cancer was approximately 4% for NS and 15% for CS; both syndromes had a cancer incidence peak in childhood. The cancers described in CFCS and NSML overlapped with those reported in NS and CS. Future epidemiologic studies will be required to confirm the described cancer spectrum and to estimate precise cancer risks.

Conservative management of endometrial hyperplasia or carcinoma with the levonorgestrel intrauterine system may be less effective in morbidly obese patients.

•Endometrial hyperplasia/carcinoma regression rates with LNG-IUS were examined by BMI.•Morbidly obese patients with EH/EHA/EC are more likely to progress.•Despite addition of oral progesterone to LNG-IUS, morbid obesity increases the odds of progression.

Undertaking a randomised controlled trial in the police setting: methodological and practical challenges.

BACKGROUND: There has been an increased drive towards Evidence Based Policing in recent years. Unlike in other public sector services, such as health and education, randomised controlled trials in the police setting are relatively rare. This paper discusses some of the methodological and practical challenges of conducting a randomised controlled trial in the police setting in the UK, based on our experience of the Connect trial. This pragmatic, cluster-randomised controlled trial investigated the effectiveness of a face-to-face training intervention for frontline officers in comparison to routine training. The primary outcome was the number of incidents which resulted in a police response reported to North Yorkshire Police control room in a 1-month period up to 6 months after delivery of training. MAIN TEXT: The methodological and practical challenges that we experienced whilst conducting the Connect trial are discussed under six headings: establishing the unit of randomisation; population of interest and sample size; co-production of evidence; time frame; outcomes; and organisational issues. CONCLUSION: Recommendations on the conduct of future randomised controlled trials in the police setting are made. To understand the context in which research is undertaken, collaboration between police and academia is needed and police officers should be embedded within trial management groups. Engagement with police data analysts to understand what data is available and facilitate obtaining trial data is also recommended. Police forces may wish to review their IT systems and recording practices. Pragmatic trials are encouraged and time frames need to allow for trial set-up and obtaining relevant ethical approvals. TRIAL REGISTRATION: ISRCTN Registry, ID: ISRCTN11685602 . Retrospectively registered on 13 May 2016.

Criteria for the safe discharge of patients from the recovery room.

Guidelines need to be in place to help nurses in the recovery room make appropriate and safe decisions when discharging patients to a surgical ward. Consciousness level, respiration, circulation, pain control, homeostasis and wound care should all be considered. Criteria from the Freeman Hospital provides practical guidance.

The Logical Grammatical Structures Test: psychometric properties and normative data in Dutch-speaking children and adolescents.

Logical grammatical structures comprehension is the ability to understand the relations between objects, actions, and qualities in spoken and written sentences. The Logical Grammatical Structures Test (LGST) was especially devised to assess these abilities in children and adolescents. In the present study the LGST was administered to 405 healthy Dutch children and adolescents. The aims of the present study were (i) to evaluate the psychometric properties of the LGST (using an Item Response Theory framework), and (ii) to establish demographically corrected normative data. The results showed that there was a strong curvilinear relationship between age and LGST performance, i.e., the relative improvement in ability level was much more pronounced for younger children (aged below 14 years) than for older children (aged above 14 years). Level of parental education was positively associated with the LGST performance. Normative data that took the relevant demographic variables into account were established, and it was shown that the LGST had sound psychometric properties.

Exposure to herbicides in house dust and risk of childhood acute lymphoblastic leukemia.

We examine the association between exposure to herbicides and childhood acute lymphoblastic leukemia (ALL). Dust samples were collected from homes of 269 ALL cases and 333 healthy controls (<8 years of age at diagnosis/reference date and residing in same home since diagnosis/reference date) in California, using a high-volume surface sampler or household vacuum bags. Amounts of agricultural or professional herbicides (alachlor, metolachlor, bromoxynil, bromoxynil octanoate, pebulate, butylate, prometryn, simazine, ethalfluralin, and pendimethalin) and residential herbicides (cyanazine, trifluralin, 2-methyl-4-chlorophenoxyacetic acid (MCPA), mecoprop, 2,4-dichlorophenoxyacetic acid (2,4-D), chlorthal, and dicamba) were measured. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression. Models included the herbicide of interest, age, sex, race/ethnicity, household income, year and season of dust sampling, neighborhood type, and residence type. The risk of childhood ALL was associated with dust levels of chlorthal; compared to homes with no detections, ORs for the first, second, and third tertiles were 1.49 (95% CI: 0.82-2.72), 1.49 (95% CI: 0.83-2.67), and 1.57 (95% CI: 0.90-2.73), respectively (P-value for linear trend=0.05). The magnitude of this association appeared to be higher in the presence of alachlor. No other herbicides were identified as risk factors of childhood ALL. The data suggest that home dust levels of chlorthal, and possibly alachlor, are associated with increased risks of childhood ALL.

The development of an extended care facility in the recovery unit: the post-anaesthesia care unit.

This article describes the development of a new service - the post-anaesthesia care unit (PACU) - that provides extended care in a recovery unit for patients who would have formerly been 'fast-tracked' through a high dependency unit (HDU). Patients requiring major surgery who stay in the recovery unit overnight are invasively monitored, have tight fluid management, blood chemistry analysis and frequently have pharmacological support. However, our overnight recovery service is not considered suitable for ventilated patients. Over 90% of patients are able to be discharged to a surgical ward within 24 hours of admission, following medical review.

Passive control of transition in three-dimensional boundary layers, with emphasis on discrete roughness elements.

A brief review of laminar flow control techniques is given and a strategy for achieving laminarization for transonic transport aircraft is discussed. A review of some flight-test results on swept-wing transition is presented. It is also shown that polished leading edges can create large regions of laminar flow because the flight environment is relatively turbulence free and the surface finish reduces the initial amplitude of the stationary crossflow vortex.

The lifestyles of affluent young people ages 9 to 15 years: a case study.

BACKGROUND: There are concerns about the future health of young people due to inactive lifestyles. However, evidence about their physical activity levels is not extensive, especially with regard to affluent young people. This study aimed to investigate whether young people from affluent backgrounds met public health recommendations for physical activity. METHODS: Diary accounts of lifestyle activity were collected from 219 students ages 9 to 15 years attending a fee-paying school in England. RESULTS: Pupils spent an average of 121 minutes per day participating in physical activities of at least moderate intensity, considerably more than public health recommendations of 60 minutes per day. However, almost a quarter of these young people engaged in less than 60 minutes of physical activity per day of at least moderate intensity. CONCLUSIONS: The picture to emerge was one of a balance between sedentary pursuits such as television and homework and physical activities such as sport and active play.

Neurotensin phase-shifts the firing rate rhythm of neurons in the rat suprachiasmatic nuclei in vitro.

The suprachiasmatic nuclei (SCN) of the hypothalamus house the main mammalian circadian pacemaker. Cell bodies in the rat SCN contain the neuropeptide neurotensin (NT), and two NT receptor types, NTS1 and nts2. Because the role of NT in the circadian rhythm processes is unknown, we studied the phase-shifting effects of NT on the firing rate rhythm of rat SCN neurons in vitro. Additionally, the NT receptor antagonists SR142948a and SR48692 were used to try and block any NT-induced phase shifts. To elucidate the second messenger pathway responsible for mediating the phase-resetting actions of NT, we utilized the phospholipase C (PLC) and protein kinase A (PKA) inhibitors U-73122 and KT5720, respectively. Application of NT during the projected day resulted in a large advance in the time of peak in FRR, whereas treatments during the projected night had no effect. Both NT receptor antagonists blocked the NT-induced phase shifts, as did the PLC inhibitor U-73122. The PKA inhibitor KT5720 had no influence on the magnitude of the phase shift caused by NT during the middle of the projected day. These results provide the first evidence that NT may play a role in regulating the rat circadian pacemaker, using NTS1 and nts2 receptors presumably coupled to PLC.

The mouse VPAC2 receptor confers suprachiasmatic nuclei cellular rhythmicity and responsiveness to vasoactive intestinal polypeptide in vitro.

Expression of coherent and rhythmic circadian (approximately 24 h) variation of behaviour, metabolism and other physiological processes in mammals is governed by a dominant biological clock located in the hypothalamic suprachiasmatic nuclei (SCN). Photic entrainment of the SCN circadian clock is mediated, in part, by vasoactive intestinal polypeptide (VIP) acting through the VPAC2 receptor. Here we used mice lacking the VPAC2 receptor (Vipr2-/-) to examine the contribution of this receptor to the electrophysiological actions of VIP on SCN neurons, and to the generation of SCN electrical firing rate rhythms SCN in vitro. Compared with wild-type controls, fewer SCN cells from Vipr2-/- mice responded to VIP and the VPAC2 receptor-selective agonist Ro 25-1553. By contrast, similar proportions of Vipr2-/- and wild-type SCN cells responded to gastrin-releasing peptide, arginine vasopressin or N-methyl-D-aspartate. Moreover, VIP-evoked responses from control SCN neurons were attenuated by the selective VPAC2 receptor antagonist PG 99-465. In firing rate rhythm experiments, the midday peak in activity observed in control SCN cells was lost in Vipr2-/- mice. The loss of electrical activity rhythm in Vipr2-/- mice was mimicked in control SCN slices by chronic treatment with PG 99-465. These results demonstrate that the VPAC2 receptor is necessary for the major part of the electrophysiological actions of VIP on SCN cells in vitro, and is of fundamental importance for the rhythmic and coherent expression of circadian rhythms governed by the SCN clock. These findings suggest a novel role of VPAC2 receptor signalling, and of cell-to-cell communication in general, in the maintenance of core clock function in mammals, impacting on the cellular physiology of SCN neurons.