Pregnancies in women with Turner syndrome: a retrospective multicentre UK study.

OBJECTIVE: To determine the characteristics and outcomes of pregnancy in women with Turner syndrome. DESIGN: Retrospective 20-year cohort study (2000-20). SETTING: Sixteen tertiary referral maternity units in the UK. POPULATION OR SAMPLE: A total of 81 women with Turner syndrome who became pregnant. METHODS: Retrospective chart analysis. MAIN OUTCOME MEASURES: Mode of conception, pregnancy outcomes. RESULTS: We obtained data on 127 pregnancies in 81 women with a Turner phenotype. All non-spontaneous pregnancies (54/127; 42.5%) were by egg donation. Only 9/31 (29%) pregnancies in women with karyotype 45,X were spontaneous, compared with 53/66 (80.3%) pregnancies in women with mosaic karyotype 45,X/46,XX (P < 0.0001). Women with mosaic karyotype 45,X/46,XX were younger at first pregnancy by 5.5-8.5 years compared with other Turner syndrome karyotype groups (P < 0.001), and more likely to have a spontaneous menarche (75.8% versus 50% or less, P = 0.008). There were 17 miscarriages, three terminations of pregnancy, two stillbirths and 105 live births. Two women had aortic dissection (2.5%); both were 45,X karyotype with bicuspid aortic valves and ovum donation pregnancies, one died. Another woman had an aortic root replacement within 6 months of delivery. Ten of 106 (9.4%) births with gestational age data were preterm and 22/96 (22.9%) singleton infants with birthweight/gestational age data weighed less than the tenth centile. The caesarean section rate was 72/107 (67.3%). In only 73/127 (57.4%) pregnancies was there documentation of cardiovascular imaging within the 24 months before conceiving. CONCLUSIONS: Pregnancy in women with Turner syndrome is associated with major maternal cardiovascular risks; these women deserve thorough cardiovascular assessment and counselling before assisted or spontaneous pregnancy managed by a specialist team. TWEETABLE ABSTRACT: Pregnancy in women with Turner syndrome is associated with an increased risk of aortic dissection.

Cardiovascular, obstetric and neonatal outcomes in women with previous fontan repair.

OBJECTIVES: To determine cardiovascular, obstetric and neonatal outcomes of pregnancies in women who have a Fontan circulation. METHODS: A retrospective case note review of all women with a Fontan circulation who attended the joint obstetric cardiac antenatal clinic at St Mary's Hospital, Manchester (UK) between 2004 and 2016 was performed. RESULTS: In total, there were 19 pregnancies in 9 women with a history of Fontan repair. 23 women with univentricular physiology attended in this time period. 10 pregnancies (53%) resulted in live births; 1 in a stillbirth at 31 weeks gestation and 8 in miscarriage. Cardiovascular complications occurred in 2 pregnancies (11%). There were no thrombotic events, arrhythmias, myocardial infarction, or endocarditis in the antenatal or postnatal period. Obstetric complications included miscarriage (26% first trimester, 16% second trimester), along with premature delivery (24-36+6) (80%) and fetal growth restriction (70%). The majority of women were delivered by caesarean section (60%). CONCLUSIONS: Women who become pregnant following a Fontan repair carry an increased risk of cardiovascular complications. Fetal and neonatal complication rates are high and emphasize the importance of thorough, multidisciplinary, pre-conceptual assessment and counseling to allow patients to make informed decisions regarding future pregnancy.

Effect of supervised aerobic exercise rehabilitation on physical fitness and quality-of-life in survivors of critical illness: an exploratory minimized controlled trial (PIX study).

BACKGROUND: Evidence is limited for the effectiveness of interventions for survivors of critical illness after hospital discharge. We explored the effect of an 8-week hospital-based exercise-training programme on physical fitness and quality-of-life. METHODS: In a parallel-group minimized controlled trial, patients were recruited before hospital discharge or in the intensive care follow-up clinic and enrolled 8-16 weeks after discharge. Each week, the intervention comprised two sessions of physiotherapist-led cycle ergometer exercise (30 min, moderate intensity) plus one equivalent unsupervised exercise session. The control group received usual care. The primary outcomes were the anaerobic threshold (in ml O2 kg(-1) min(-1)) and physical function and mental health (SF-36 questionnaire v.2), measured at Weeks 9 (primary time point) and 26. Outcome assessors were blinded to group assignment. RESULTS: Thirty patients were allocated to the control and 29 to the intervention. For the anaerobic threshold outcome at Week 9, data were available for 17 control vs 13 intervention participants. There was a small benefit (vs control) for the anaerobic threshold of 1.8 (95% confidence interval, 0.4-3.2) ml O2 kg(-1) min(-1). This advantage was not sustained at Week 26. There was evidence for a possible beneficial effect of the intervention on self-reported physical function at Week 9 (3.4; -1.4 to 8.2 units) and on mental health at Week 26 (4.4; -2.4 to 11.2 units). These potential benefits should be examined robustly in any subsequent definitive trial. CONCLUSIONS: The intervention appeared to accelerate the natural recovery process and seems feasible, but the fitness benefit was only short term. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ISRCTN65176374 (http://www.controlled-trials.com/ISRCTN65176374).

Effects of chronic heat stress on plasma concentration of secreted heat shock protein 70 in growing feedlot cattle.

Sixty Angus steers (449.2±11.0 kg) with implanted body temperature (BT) transmitters were used in a 110-d study to determine the effect of chronic stress (housing, diet, and climate) on extracellular heat shock protein 70 (eHsp70) concentration in plasma. The steers were a subset of a larger study involving 164 steers. Before the start of the study (d -31), 63 steers were implanted with a BT transmitter between the internal abdominal muscle and the peritoneum at the right side flank. Steers were housed in 20 pens (10 with shade and 10 without). Within each pen, 3 steers had a transmitter, and BT was recorded at 30-min intervals throughout the study. On d 0, 30, 60, 90, and 110, steers were weighed, BCS assessed (1 to 9 scale in which 1=emaciated and 9=obese), and 10 mL of blood from the coccygeal vein was collected for determination of inducible heat shock protein 70 (Hsp70) concentration by ELISA. Climatic variables (ambient temperature, relative humidity, solar radiation, black globe temperature, and wind speed) were obtained every 30 min from an on-site weather station. The relationship between the climatic variables and Hsp70 concentration were examined. As we failed to detect an effect of shade, all data were pooled. Mean BT over the duration of the study was 39.6±0.10°C. Mean BT was lowest (38.7±0.10°C) on d 0 and highest on d 110 (40.2°C±0.10). The Hsp70 concentration was least on d 0 (2.33±0.47 ng/mL) and greatest on d 30 (8.08±0.78 ng/mL). The Hsp70 concentration decreased from d 30 but remained above the d-0 concentrations on d 60, 90, and 110. There was a strong relationship between Hsp70 concentration and ambient temperature (r2=0.86; P<0.0001) and Hsp70 concentration and photoperiod (r2=0.94; P<0.0001) and no relationship with BT (r2=0.06; P<0.0001). When assessed with both BCS and BT, the relationship was moderate (r2=0.48; P<0.001). The relationship between Hsp70 and change in BT (BTΔ) above 38.6°C was also moderate (r2=0.54; P<0.0001). The BT at a given time does not appear to be related to Hsp70 concentration. However, Hsp70 expression may be a useful indictor for BTΔ when BT>38.6°C. The Hsp70 concentration is a reliable indicator of chronic stress but is not a reliable indicator of a single stressor when animals are exposed to multiple chronic stressors.

Effect of shade on body temperature and performance of feedlot steers.

A 120-d feedlot study using 164 Angus steers (BW = 396.7 ± 7.0 kg) was undertaken in Queensland Australia (24°84' S, 149°78' N) to determine the effect of shade on body temperature (T(B)) and performance. Cattle were allocated to 20 pens: 16 with an area of 144 m(2) (8 steers/pen) and 4 with an area of 168 m(2) (9 steers/pen). Treatments (10 pens/treatment) were unshaded (NS) vs. shaded (SH). Shade (3.3 m(2)/steer) was provided by 80% solar block shade cloth. Before the study (d -31), 63 steers were implanted (between the internal abdominal muscle and the peritoneum at the right side flank) with a T(B) transmitter. Within each pen, 3 steers had a T(B) transmitter. Individual T(B) was obtained every 30 min. The cattle were fed a feedlot diet and had ad libitum access to water. Water usage and DMI were recorded daily on a pen basis. Average daily gain and G:F were calculated on a pen basis. Climatic variables were obtained from an on-site weather station every 30 min. Individual panting scores (PS) were obtained daily at 0600, 1200, and 1600 h. From these, mean PS (MPS) were calculated for each pen. At slaughter (d 121), individual HCW, loin muscle area (LMA), rump fat depth (P8), 12th-rib fat depth, and marbling score were obtained. Mean T(B) was not affected (P > 0.05) by treatment (SH = 39.58°C; NS = 39.60°C). However, during a 21-d heat wave when cattle were exposed to a mean ambient temperature (T(AM)) > 30°C for 8 h each d (T(AM) between 0800 and 1800 h = 29.7°C, and 23.4°C between 1830 and 0730 h), the T(B) of SH steers (40.41 ± 0.10°C) was less (P < 0.01) than the T(B) of NS steers (41.14 ± 0.10°C). During this period, pen-MPS were greater (P < 0.05) for the NS cattle at all observation times. Over the first 6 d of the heat wave, MPS of NS steers at 1200 h was 2.47 (P < 0.01) vs. 1.39 for SH steers. Hip height, DMI, ADG, and G:F were greater (P < 0.05) for SH cattle. Exit BW (final BW) of SH steers (596.1 kg) was greater (P < 0.05) when compared with NS steers (578.6 kg). During the heat wave, DMI was 51% less for NS steers and 39% less for SH steers when compared with the pre-heat wave period (P < 0.01). The HCW of SH steers (315.4 ± 0.8 kg) was greater (P < 0.05) than for NS steers (321.4 ± 0.8 kg). No treatment differences (P > 0.05) were found for LMA, P8, or marbling score. Access to shade improved (P < 0.05) ADG and G:F, increased HCW, and decreased MPS; however, shade did not completely eliminate the impact of high heat load.

An extension of the Cormack-Jolly-Seber model for continuous covariates with application to Microtus pennsylvanicus.

Recent developments in the Cormack-Jolly-Seber (CJS) model for analyzing capture-recapture data have focused on allowing the capture and survival rates to vary between individuals. Several methods have been developed in which capture and survival are functions of auxiliary variables that may be discrete, constant over time, or apply to the population as a whole, but the problem has not been solved for continuous covariates that vary with both time and individual. This article proposes a new method to handle such covariates by modeling changes over time via a diffusion process and using logistic functions to link the variable to the CJS capture and survival rates. Bayesian methods are used to estimate the model parameters. The method is applied to study the effect of body mass on the survival of the North American meadow vole, Microtus pennsylvanicus.

Experiences of families when a relative is diagnosed brain stem dead: understanding of death, observation of brain stem death testing and attitudes to organ donation.

Brain stem death may be a difficult concept for relatives to understand. Our ITU practice follows published recommendations that the use of explanatory leaflets showing CT scans and observing brain stem death testing in some cases may help relatives to understand that death has occurred. Using this strategy, we interviewed 27 relatives 12 months after bereavement following certification by brain stem testing, investigating their understanding of brain stem death, subsequent attitudes to organ donation, grief reactions and attitudes of those who had observed the tests. Most relatives understood that the brain stem death tests indicated that survival was not possible, although three relatives had not fully understood this and valued the opportunity to discuss it again. Only five relatives observed the tests, all were pleased that they had done so as this had confirmed their understanding that death had occurred; however, these relatives had more evidence of psychological distress. No relatives who agreed to organ donation regretted this but three who did not allow donation subsequently expressed regret. Several relatives thought that observing the tests would have helped them to understand that death had occurred, making easier the decision to allow organ donation.

UK guidance for non-heart-beating donation.

This guidance offers consensus opinion on the optimum management of non-heart-beating organ donation in adult critical care units. The guidance is not meant to dictate practice but rather to offer suggestions as to what might be considered reasonable practice. The following sections mainly relate to the medical aspects of non-heart-beating organ donation. Fuller guidance on other aspects of organ and tissue donation is available on the Society's website (www.ics.ac.uk). There are a number of parallel areas of work, such as the law on consent, the definition of death and revision of the original Code of Practice describing brainstem testing, which means that many aspects of organ donation are changing rapidly. This guidance is designed to help critical care practitioners while these issues are resolved.

A randomized controlled trial of home telecare.

We have established a randomized controlled trial of home telecare. The intervention aims to address a growing problem in the National Health Service (NHS), that is, high admission rates of patients with exacerbations of chronic obstructive pulmonary disease (COPD). Equipment procurement for the trial has been difficult, as no single supplier was able to meet the project s full requirements. The fact that the service is provided by existing clinical NHS staff has advantages when considering the generalizability of the results within the NHS. However, there are also disadvantages, since existing staff have little research experience. Considerable time has been required to help staff familiarize themselves with the equipment and become comfortable with its use. This has posed a barrier to the implementation of the service.

Are the proposed limits of energy intake:basal metabolic rate and dietary nitrogen:urinary nitrogen ratios suitable for validation of food intake?

The validity of 7 d weighed records of diet obtained for pre-menopausal Mexican women was assessed by two independent methods: the energy intake:BMR (EI:BMR) and the dietary N:urinary N (DN:UN). For the latter, complete urine collections are required and completeness was assessed from measurements of para-aminobenzoic acid (PABA) excretion. There were forty-six adult female subjects in the study, thirty-four were from Mexico City and twelve were from a rural population in the Central Highlands, Mexico. However, data were rejected from five urban women for whom the PABA excretion data suggested incomplete urine collection on four or more days. BMR was measured with Oxylog portable O2 consumption meters, and physical activity level was assessed from a self-completed activity diary. An approximate relationship between the EI:BMR ratio and the DN:UN ratio suggested that the rejection limits on the EI:BMR ratio recommended by are wider than the limits on the DN:UN ratio recommended by. Using the recommended cut-off points for EI:BMR but wider limits for DN:UN, twenty-one and twenty-five women respectively had acceptable intake records by the two methods, and sixteen of them by both methods. In conclusion the modification of the DN:UN limits to 0.92 and 1.70 to set acceptable intake values makes the use of measurements of N and energy balance comparable. Urine values with PABA recoveries greater than should be rejected, as should UN values validated by less than 3 d.

Activation of extracellular signal-related protein kinases 1 and 2 of the mitogen-activated protein kinase family by lipopolysaccharide requires plasma in neutrophils from adults and newborns.

Neutrophils exposed to low concentrations of gram-negative lipopolysaccharide (LPS) become primed and have an increased oxidative response to a second stimulus (e.g., formyl-methionyl-leucyl-phenylalanine [fMLP]). In studies aimed at understanding newborn sepsis, we have shown that neutrophils of newborns are not primed in response to LPS. To further understand the processes involved in LPS-mediated priming of neutrophils, we explored the role of extracellular signal-related protein kinases (ERK 1 and 2) of the mitogen-activated protein kinase family. We found that LPS activated ERK 1 and 2 in cells of both adults and newborns and that activation was plasma dependent (maximal at > or =5%) through LPS-binding protein. Although fibronectin in plasma is required for LPS-mediated priming of neutrophils of adults assessed by fMLP-triggered oxidative burst, it was not required for LPS-mediated activation of ERK 1 and 2. LPS-mediated activation was dose and time dependent; maximal activation occurred with approximately 5 ng of LPS per ml and at 10 to 40 min. We used the inhibitor PD 98059 to study the role of ERK 1 and 2 in the LPS-primed fMLP-triggered oxidative burst. While Western blotting showed that 100 microM PD 98059 completely inhibited LPS-mediated ERK activation, oxidative response to fMLP by a chemiluminescence assay revealed that the same concentration inhibited the LPS-primed oxidative burst by only 40%. We conclude that in neutrophils, LPS-mediated activation of ERK 1 and 2 requires plasma and that this activation is not dependent on fibronectin. In addition, we found that the ERK pathway is not responsible for the lack of LPS priming in neutrophils of newborns but may be required for 40% of the LPS-primed fMLP-triggered oxidative burst in cells of adults.

Wound botulism in drug addicts in the United Kingdom.

Clostridium novyi has recently been identified as the causative organism responsible for the deaths of 35 heroin addicts who had injected themselves intramuscularly. We present two heroin addicts who developed C. botulinum infection following intramuscular or subcutaneous injection of heroin. Like C. novyi, this grows under anaerobic conditions and clinical presentation may be similar; however, descending motor or autonomic signs are invariably present in botulism. The prognosis is good if the diagnosis is made early and appropriate treatment commenced.

Collaboration among community members, local health service providers, and researchers in an urban research center in Harlem, New York.

The Urban Research Center at the Center for Urban Epidemiologic Studies brings together community members and researchers working in Harlem, New York. A Community Advisory Board (CAB) composed of community members, service providers, public health professionals, and researchers was formed to assist the Center's research and interventions and to guide community partnerships. Through a collaborative process, the CAB identified three public health problems-substance use, infectious diseases, and asthma-as action priorities. To deal with substance use, the Center created a Web-based resource guide for service providers and a "survival guide" for substance users, designed to improve access to community services. To deal with infectious diseases, the Center is collaborating with local community-based organizations on an intervention that trains injection drug users to serve as peer mentors to motivate behavior change among other injection drug users. To deal with asthma, the Center is collaborating with community child care providers on an educational intervention to increase asthma awareness among day care teaching staff, enhance communication between staff and families, and improve the self-management skills of children with asthma. The Center's experience has demonstrated that active communities and responsive researchers can establish partnerships that improve community health.

"Hospital at home" versus hospital care in patients with exacerbations of chronic obstructive pulmonary disease: prospective randomised controlled trial.

OBJECTIVES: To compare "hospital at home" and hospital care as an inpatient in acute exacerbations of chronic obstructive pulmonary disease. DESIGN: Prospective randomised controlled trial with three months' follow up. SETTING: University teaching hospital offering secondary care service to 350 000 patients. PATIENTS: Selected patients with an exacerbation of chronic obstructive pulmonary disease where hospital admission had been recommended after medical assessment. INTERVENTIONS: Nurse administered home care was provided as an alternative to inpatient admission. MAIN OUTCOME MEASURES: Readmission rates at two weeks and three months, changes in forced expiratory volume in one second (FEV(1)) from baseline at these times and mortality. RESULTS: 583 patients with chronic obstructive pulmonary disease referred for admission were assessed. 192 met the criteria for home care, and 42 refused to enter the trial. 100 were randomised to home care and 50 to hospital care. On admission, FEV(1) after use of a bronchodilator was 36.1% (95% confidence interval 2.4% to 69.8%) predicted in home care and 35.1% (6.3% to 63. 9%) predicted in hospital care. No significant difference was found in FEV(1 )after use of a bronchodilator at two weeks (42.6%, 3.4% to 81.8% versus 42.1%, 5.1% to 79.1%) or three months (41.5%, 8.2% to 74.8% versus 41.9%, 6.2% to 77.6%) between the groups. 37% of patients receiving home care and 34% receiving hospital care were readmitted at three months. No significant difference was found in mortality between the groups at three months (9% versus 8%). CONCLUSIONS: Hospital at home care is a practical alternative to emergency admission in selected patients with exacerbations of chronic obstructive pulmonary disease.