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1.
Nutrients ; 12(5)2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32429481

RESUMO

High levels of storage iron may increase malaria susceptibility. This risk has not been investigated in semi-immune adolescents. We investigated whether baseline iron status of non-pregnant adolescent girls living in a high malaria transmission area in Burkina Faso affected malaria risk during the following rainy season. For this prospective study, we analysed data from an interim safety survey, conducted six months into a randomised iron supplementation trial. We used logistic regression to model the risk of P. falciparum infection prevalence by microscopy, the pre-specified interim safety outcome, in relation to iron status, nutritional indicators and menarche assessed at recruitment. The interim survey was attended by 1223 (82%) of 1486 eligible participants, 1084 (89%) of whom were <20 years at baseline and 242 (22%) were pre-menarcheal. At baseline, prevalence of low body iron stores was 10%. At follow-up, 38% of adolescents had predominantly asymptomatic malaria parasitaemias, with no difference by menarcheal status. Higher body iron stores at baseline predicted an increased malaria risk in the following rainy season (OR 1.18 (95% CI 1.05, 1.34, p = 0.007) after adjusting for bed net use, age, menarche, and body mass index. We conclude that routine iron supplementation should not be recommended without prior effective malaria control.

2.
BMJ Open Qual ; 9(2)2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32327423

RESUMO

INTRODUCTION: The UK Department of Health have targeted a reduction in stillbirth by 50% by 2025; to achieve this, the first version of the Saving Babies' Lives Care Bundle (SBLCB) was developed by NHS England in 2016 to improve four key areas of antenatal and intrapartum care. Clinical practice guidelines are a key means by which quality improvement initiatives are disseminated to front-line staff. METHODS: Seventy-five clinical practice guidelines covering the four areas of antenatal and intrapartum care in the first version of SBLCB were obtained from 19 maternity providers. The content and quality of guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Maternity health professionals in participating organisations were invited to participate in an anonymous survey to determine perceptions toward and experiences of the use of clinical practice guidelines using a series of Likert scales. RESULTS: Unit guidelines showed considerable variation in quality with median scores of 50%-58%. Only 4 (5.6%) guidelines were recommended for use in clinical practice without modifications, 54 (75.0%) were recommended for use subject to modifications and 12 (16.7%) were not recommended for use. The lowest scoring domains were 'rigour of development', 'stakeholder involvement' and 'applicability'. A significant minority of unit guidelines omitted recommendations from national guidelines. The majority of staff believed that clinical practice guidelines standardised and improved the quality of care but over 30% had insufficient time to use them and 24% stated they were unable to implement recommendations. CONCLUSION: To successfully implement initiatives such as the SBLCB change is needed to local clinical practice guidelines to reduce variation in quality and to ensure they are consistent with national recommendations . In addition, to improve clinical practice, adequate time and resources need to be in place to deliver and evaluate care recommended in the SBLCB.

3.
J Hum Genet ; 65(6): 531-539, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32152366

RESUMO

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is predominantly caused by heterozygous missense variants in the cardiac ryanodine receptor, RYR2. However, many RYR2 missense variants are classified as variants of uncertain significance (VUS). We systematically re-evaluated all RYR2 variants in healthy individuals and those with CPVT or arrhythmia using the 2015 American College of Medical Genomics guidelines. RYR2 variants were identified by the NW Genomic Laboratory Hub, from the published literature and databases of sequence variants. Each variant was assessed based on minor allele frequencies, in silico prediction tools and appraisal of functional studies and classified according to the ACMG-AMP guidelines. Phenotype data was collated where available. Of the 326 identified RYR2 missense variants, 55 (16.9%), previously disease-associated variants were reclassified as benign. Application of the gnomAD database of >140,000 controls allowed reclassification of 11 variants more than the ExAC database. CPVT-associated RYR2 variants clustered predominantly between amino acid positions 3949-4332 and 4867-4967 as well as the RyR and IP3R homology-associated and ion transport domains (p < 0.005). CPVT-associated RYR2 variants occurred at more conserved amino acid positions compared with controls, and variants associated with sudden death had higher conservation scores (p < 0.005). There were five potentially pathogenic RYR2 variants associated with sudden death during sleep which were located almost exclusively in the C-terminus of the protein. In conclusion, control sequence databases facilitate reclassification of RYR2 variants but the majority remain as VUS. Notably, pathogenic variants in RYR2 are associated with death in sleep.

4.
Hum Fertil (Camb) ; : 1-7, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32098536

RESUMO

Time-lapse (TL) incubators are increasingly used in in vitro fertilization (IVF) laboratories but there have been few studies of their effectiveness in comparison to other incubator types. Moreover, the design of most studies has been limited by the quality of the control incubator. We have therefore performed a one-year pseudo-randomized prospective study of IVF cycles using a TL incubator (EmbryoScope™) (n = 243) or a conventional incubator (K-System G-185 Flatbed) (n = 203). The two groups were well matched in terms of clinical parameters: IVF cycle attempt number, IVF/ICSI, age, number and day (3 or 5) of embryo transfer. Embryos were selected for transfer using conventional (non-TL) morphological grading. The EmbryoScope group had an increased chance of a live birth (43.2% vs. 34.5%; OR = 1.43 [95%CI: 0.96-2.13]) with significantly reduced early pregnancy loss (5.8% vs. 13.8%; OR = 0.37 [0.19-0.74]) compared to the K-System incubator. There was a higher proportion of 4-cell embryos on day 2 and 8-cell embryos on day 3 in the EmbryoScope, compared to the K-Systems. The use of TL incubators is appropriate in ART by virtue of their high specification, facility for low oxygen culture and provision of minimally disturbed culture conditions which limit exposure of human embryos to environmental stress.

5.
J Paediatr Child Health ; 56(6): 878-883, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31916647

RESUMO

AIM: This study describes the prevalence and severity of perceived fatigue in a young neurofibromatosis type 1 (NF1) population. METHODS: Ethical approval was obtained and NF1 affected Individuals aged 2-18 years from the Manchester's NF1 clinic invited along with any unaffected siblings. The PedsQL Multidimensional Fatigue Scale Parental and child report was used. This validated measure explores cognitive, physical and sleep/rest domains on a 0-100 scale. Higher scores indicate less fatigue. Fatigue scores in affected children were compared to unaffected siblings after adjusting for age, sex and Index of Multiple Deprivation and with published population standards using z-scores. RESULTS: A total of 286 families were invited and 75 affected and 16 siblings participated. There were significant differences between NF1 and controls in the aggregated fatigue core (child report 55 ± 19 vs. 75 (14), P < 0.001; parent 54 ± 20 vs. 73 ± 18, P = 0.001) and the three sub-domains: cognitive (child 48 ± 27 vs. 75 ± 23, P < 0.001), physical (child 59 ± 19 vs. 82 ± 14, P < 0.001) and sleep/rest (child 59 ± 19 vs. 71 ± 15, P = 0.018). Similar differences were seen when compared with published controls (aggregated child z-score -1.9 ± 1.4, P < 0.001; parent -3.2 ± 1.8, P < 0.001). Prevalence of severe fatigue indicated by scores <2 standard deviation below published means for healthy controls were also higher for children with NF on both parent and child reports. Agreement between child and parent reports were limited as is frequently seen in the literature. CONCLUSION: This study suggests that children with NF1 are affected by perceived fatigue when compared with healthy children who do not have NF1.

6.
Clin Nutr ; 39(1): 204-214, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30737046

RESUMO

BACKGROUND & AIMS: Low iron stores may protect from malaria infection, therefore improving iron stores in early pregnancy in line with current recommendations could increase malaria susceptibility. To test this hypothesis we compared iron biomarkers and red cell indices in nulliparae and primigravidae who participated in a randomized controlled trial of long-term weekly iron supplementation. METHODS: Cross-sectional and longitudinal data analysis from a randomized controlled trial of long-term weekly iron supplementation in rural Burkina Faso. Malaria parasitaemia was monitored and biomarkers and red cell indices measured at study end-points: plasma ferritin, transferrin receptor (sTfR), zinc protoporphyrin, hepcidin, sTfR/log10 ferritin ratio, body iron, haemoglobin, red cell distribution width; mean corpuscular haemoglobin concentration/volume, and C-reactive protein. Correlation coefficients between biomarkers and red cell indices were determined. A regression correction approach based on ferritin was used to estimate iron body stores, allowing for inflammation. Body iron differences were compared between nulliparae and primigravidae, and the association determined of iron biomarkers and body iron stores with malaria. RESULTS: Iron and haematological indices of 972 nulliparae (mean age 16.5 years) and 314 primigravidae (median gestation 18 weeks) were available. Malaria prevalence was 54.0% in primigravidae and 41.8% in nulliparae (relative risk 1.28, 95% CI 1.13-1.45, P < 0.001), anaemia prevalence 69.7% and 43.4% (P < 0.001), and iron deficient erythropoiesis (low body iron) 8.0% and 11.7% (P = 0.088) respectively. Unlike other biomarkers the sTfR/log10 ferritin ratio showed no correlation with inflammation as measured by CRP. Most biomarkers indicated reduced iron deficiency in early pregnancy, with the exception of haemoglobin. Body iron increased by 0.6-1.2 mg/kg in early gestation, did not differ by malaria status in nulliparae, but was higher in primigravidae with malaria (6.5 mg/kg versus 5.0 mg/kg; relative risk 1.53, 95% CI 0.67-2.38, P < 0.001). CONCLUSION: In primigravidae, early pregnancy haemoglobin was not a good indicator of requirement for iron supplementation, which could be detrimental given the association of better iron status with increased malaria infection. TRIAL REGISTRATION: clinicaltrials.gov:NCT01210040. Until placed in a public repository, data relating to the current study can be requested from the corresponding author and will be made available following an end user data agreement and sponsor approval.

7.
Malar J ; 18(1): 374, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771607

RESUMO

BACKGROUND: In view of recent evidence from a randomized trial in Burkina Faso that periconceptional iron supplementation substantially increases risk of spontaneous preterm birth (< 37 weeks) in first pregnancies (adjusted relative risk = 2.22; 95% CI 1.39-3.61), explanation is required to understand potential mechanisms, including progesterone mediated responses, linking long-term iron supplementation, malaria and gestational age. METHODS: The analysis developed a model based on a dual hit inflammatory mechanism arising from simultaneous malaria and gut infections, supported in part by published trial results. This model is developed to understand mechanisms linking iron supplementation, malaria and gestational age. Background literature substantiates synergistic inflammatory effects of these infections where trial data is unavailable. A path modelling exercise assessed direct and indirect paths influencing preterm birth and gestation length. RESULTS: A dual hit hypothesis incorporates two main pathways for pro-inflammatory mechanisms, which in this model, interact to increase hepcidin expression. Trial data showed preterm birth was positively associated with C-reactive protein (P = 0.0038) an inflammatory biomarker. The malaria pathway upregulates C-reactive protein and serum hepcidin, thereby reducing iron absorption. The enteric pathway results from unabsorbed gut iron, which induces microbiome changes and pathogenic gut infections, initiating pro-inflammatory events with lipopolysaccharide expression. Data from the trial suggest that raised hepcidin concentration is a mediating catalyst, being inversely associated with shorter gestational age at delivery (P = 0.002) and positively with preterm incidence (P = 0.007). A segmented regression model identified a change-point consisting of two segments before and after a sharp rise in hepcidin concentration. This showed a post change hepcidin elevation in women with increasing C-reactive protein values in late gestation (post-change slope 0.55. 95% CI 0.39-0.92, P < 0.001). Path modelling confirmed seasonal malaria effects on preterm birth, with mediation through C-reactive protein and (non-linear) hepcidin induction. CONCLUSIONS: Following long-term iron supplementation, dual inflammatory pathways that mediate hepcidin expression and culminate in progesterone withdrawal may account for the reduction in gestational age observed in first pregnancies in this area of high malaria exposure. If correct, this model strongly suggests that in such areas, effective infection control is required prior to iron supplementation to avoid increasing preterm births. Trial registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010.


Assuntos
Gastroenteropatias/etiologia , Ferro/administração & dosagem , Malária/parasitologia , Nascimento Prematuro/epidemiologia , Adolescente , Burkina Faso , Suplementos Nutricionais/análise , Feminino , Humanos , Modelos Teóricos , Nascimento Prematuro/etiologia , Risco , Adulto Jovem
8.
Ophthalmic Physiol Opt ; 39(6): 432-440, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31602674

RESUMO

PURPOSE: A vignette study to examine treatment decisions made by UK hospital optometrists in patients with neovascular age-related macular degeneration (nAMD) and the effect of optometrists' experience on agreement. METHODS: Patients with nAMD attending Manchester Royal Eye Hospital, Manchester, UK were identified as potential candidates for the case series of vignettes. The cases were chosen to reflect a varied case-mix with respect to difficulty as well as ensuring good quality of the images. Each vignette included a history summary consisting of the number of previous injections given and visual acuity measurements at baseline, the previous visit, and the current visit. Images were compiled to show baseline fundus photographs and ocular coherence tomography (OCT) images with the current visit images on which the treatment decision was to be made along with the images from the previous visit. Hospital optometrists were recruited and asked to complete the series of vignettes, deciding if treatment was required at that visit and how confident they felt with that decision. Their responses were compared to the reference standard created by a consensus of consultant ophthalmologists with a sub-speciality interest in medical retina. RESULTS: Regarding treatment decision for optometrists, the percentage correct value was 75% with the sensitivity being 75.6% (95% CI 70.1-80.3) and the specificity as 75.1% (95% CI 72.1-77.8). No statistically significant difference was found between differing levels of experience. However, there was a significant difference in confidence levels between groups. Potentially sight threatening decisions accounted for 6.4% of the optometrists' decisions, 3.5% were made with a high confidence rating suggesting no discussion with an ophthalmologist was required. CONCLUSIONS: Although the optometrists showed modest agreement with the reference standard in a series of cases that have higher than average complexity, the optometrists showed a similar amount of variability within their treatment decisions compared to the reference standard. The optometrists were therefore not inferior in their performance compared to the ophthalmologists and this can be seen as supporting evidence for their extended role within this clinical area. Experience did not have an effect on 'correct' treatment decisions although there was a statistically significant effect on increasing confidence of treatment decision.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Competência Clínica , Tomada de Decisões , Hospitais , Oftalmologistas/normas , Optometristas/normas , Degeneração Macular Exsudativa/tratamento farmacológico , Humanos , Injeções Intravítreas , Curva ROC , Tomografia de Coerência Óptica , Reino Unido , Degeneração Macular Exsudativa/diagnóstico
9.
Malar J ; 18(1): 161, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060615

RESUMO

BACKGROUND: Iron supplementation before a first pregnancy may improve the future health of mother and baby by reducing maternal anaemia. Iron supplementation could, however, increase malaria infections, notably in primigravidae who are most susceptible. The pathogenicity of other iron-utilizing pathogens could also increase, causing inflammation leading to increased risk of adverse birth outcomes. This paper reports pre-specified secondary birth outcomes from a safety trial in Burkina Faso in an area of high malaria endemicity. Primary outcomes from that trial had investigated effects of long-term weekly iron supplementation on malaria and genital tract infections in non-pregnant and pregnant women. METHODS: A double-blind, randomized controlled trial. Nulliparous, mainly adolescent women, were individually randomized periconceptionally to receive weekly either 60 mg elemental iron and 2.8 mg folic acid, or 2.8 mg folic acid alone, continuing up to the first antenatal visit for those becoming pregnant. Secondary outcomes were ultrasound-dated gestational age, fetal growth, placental malaria, chorioamnionitis and iron biomarkers. Seasonal effects were assessed. Analysis was by intention to treat. RESULTS: 478 pregnancies occurred to 1959 women: 258/980 women assigned iron and folic acid and 220/979 women assigned folic acid alone. Malaria prevalence at the first antenatal visit was 53% (iron) and 55% (controls). Mean birthweight was 111 g lower in the iron group (95% CI 9:213 g, P = 0.033). Mean gestational ages were 264 days (iron) and 269 days (controls) (P = 0.012), with 27.5% under 37 weeks compared to 13.9% in controls (adjRR = 2.22; 95% CI 1.39-3.61) P < 0.001). One-third of babies were growth restricted, but incidence did not differ by trial arm. Half of placentae had evidence of past malaria infection. C-reactive protein > 5 mg/l was more common prior to births < 37 weeks (adjRR = 2.06, 95% CI 1.04-4.10, P = 0.034). Preterm birth incidence during the rainy season was ~ 50% in the iron arm and < 20% in controls (P = 0.001). Chorioamnionitis prevalence peaked in the dry season (P = 0.046), with no difference by trial arm (P = 0.14). CONCLUSION: Long-term weekly iron supplementation given to nulliparous women in a malaria endemic area was associated with higher risk of preterm birth in their first pregnancy. Trial Registration NCT01210040. Registered with Clinicaltrials.gov on 27th September 2010.


Assuntos
Suplementos Nutricionais/efeitos adversos , Ferro/administração & dosagem , Malária/epidemiologia , Fenômenos Fisiológicos da Nutrição Materna , Nascimento Prematuro/etiologia , Adolescente , Peso ao Nascer/efeitos dos fármacos , Burkina Faso/epidemiologia , Método Duplo-Cego , Doenças Endêmicas , Feminino , Ácido Fólico/administração & dosagem , Idade Gestacional , Humanos , Recém-Nascido , Ferro/efeitos adversos , Malária/complicações , Micronutrientes/administração & dosagem , Micronutrientes/efeitos adversos , Gravidez , Nascimento Prematuro/epidemiologia , Prevalência , Fatores de Risco , Adulto Jovem
10.
Hum Reprod ; 34(5): 920-931, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30868153

RESUMO

STUDY QUESTION: Has birthweight (BW) changed over time among IVF-conceived singletons? SUMMARY ANSWER: Singleton BW has increased markedly over the past 25 years. WHAT IS KNOWN ALREADY: IVF conceived singletons have had a higher incidence of low BW compared to spontaneously conceived singletons, and this has raised concerns over long-term increased risks of cardio-metabolic disease. However, few causal links between IVF procedures and BW have been robustly established, and few studies have examined whether BW has changed over time as IVF techniques have developed. STUDY DESIGN, SIZE, DURATION: A total of 2780 live born singletons conceived via IVF or ICSI treated in the reproductive medicine department of a single publicly funded tertiary care centre between 1991 and 2015 were included in this retrospective study. The primary outcome measure was singleton BW adjusted for gestational age, maternal parity and child gender. Multivariable linear regression models were used to estimate the associations between patient prognostic factors and IVF treatment procedures with adjusted BW. PARTICIPANTS/MATERIALS, SETTING, METHODS: All singletons conceived at the centre following IVF/ICSI using the mother's own oocytes, and non-donated fresh or frozen/thawed embryos with complete electronic data records, were investigated. Available electronic records were retrieved from the Human Fertilization and Embryology Authority for dataset collation. Multiple linear regression analysis was used to evaluate associations between IVF treatment parameters and BW, after adjusting for the year of treatment and patient characteristics and pregnancy factors. MAIN RESULTS AND THE ROLE OF CHANCE: In the primary multivariable model, singleton BW increased by 7.4 g per year (95% CI: 3.2-11.6 g, P = 0.001), an increase of close to 180 g throughout the 25-year period after accounting for gestational age, maternal parity, child gender, IVF treatment parameters, patient prognostic characteristics and pregnancy factors. Fresh and frozen embryo transfer-conceived singletons showed a similar increase in BW. Frozen/thawed embryo transfer conceived singletons were on average 53 g heavier than their fresh embryo conceived counterparts (95% CI: 3.7-103.3 g, P = 0.035). LIMITATIONS, REASONS FOR CAUTION: The independent variables included in the study were limited to those that have been consistently recorded and stored electronically over the past two decades. WIDER IMPLICATIONS OF THE FINDINGS: There has been a progressive BW increase in IVF singletons over time in one large centre with consistent treatment eligibility criteria. Such a change is not seen in the general population of live born singletons in the UK or other developed countries, and seems to be specific to this IVF population. This may be a reflection of changes in practice such as undisturbed extended embryo culture to the blastocyst stage, optimized commercial culture media composition, single embryo transfer and ICSI. Moreover, singletons conceived from frozen/thawed embryos had higher birth weights when compared to their fresh embryo transfer counterparts. The causal pathway is unknown; however, it could be due to the impact on embryos of the freeze/thaw process, self-selection of embryos from couples who produce a surplus of embryos, and/or embryo replacement into a more receptive maternal environment. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the EU FP7 project grant, EpiHealthNet (FP7-PEOPLE-2012-ITN-317146). The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

11.
Br J Ophthalmol ; 103(8): 1066-1071, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30309913

RESUMO

BACKGROUND: Glaucoma referral filtering schemes have operated in the UK for many years. However, there is a paucity of data on the false-negative (FN) rate. This study evaluated the clinical effectiveness of the Manchester Glaucoma Enhanced Referral Scheme (GERS), estimating both the false-positive (FP) and FN rates. METHOD: Outcome data were collected for patients newly referred through GERS and assessed in 'usual-care' clinics to determine the FP rate (referred patients subsequently discharged at their first visit). For the FN rate, glaucoma suspects deemed not requiring referral following GERS assessment were invited to attend for a 'reference standard' examination including all elements of assessment recommended by National Institute for Health and Care Excellence (NICE) by a glaucoma specialist optometrist. A separate 33 cases comprising randomly selected referred and non-referred cases were reviewed independently by two glaucoma specialist consultant ophthalmologists to validate the reference standard assessment. RESULTS: 1404 patients were evaluated in GERS during the study period; 651 (46.3%) were referred to the Hospital Eye Service (HES) and 753 (53.6%) were discharged. The FP rate in 307 assessable patients referred to the HES was 15.5%. This study reviewed 131 (17.4%) of those patients not referred to the HES through the GERS scheme; 117 (89.3%) were confirmed as not requiring hospital follow-up; 14 (10.7%) required follow-up, including 5 (3.8%) offered treatment. Only one patient (0.8%) in this sample met the GERS referral criteria and was not referred (true FN). There were no cases of missed glaucoma or non-glaucomatous pathology identified within our sample. CONCLUSION: The Manchester GERS is an effective glaucoma filtering scheme with a low FP and FN rate.


Assuntos
Glaucoma/diagnóstico , Pressão Intraocular/fisiologia , Seleção Visual/métodos , Campos Visuais/fisiologia , Adulto , Feminino , Seguimentos , Glaucoma/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
BMC Med ; 16(1): 224, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30482203

RESUMO

BACKGROUND: Birth weight and early child growth are important predictors of long-term cardiometabolic disease risk, in line with the Developmental Origins of Health and Disease hypothesis. As human assisted reproductive technologies (ARTs) occur during the sensitive periconceptional window of development, it has recently become a matter of urgency to investigate risk in ART-conceived children. METHODS: We have conducted the first large-scale, national cohort study of early growth in ART children from birth to school age, linking the register of ART, held by the UK's Human Fertilisation and Embryology Authority, to Scottish maternity and child health databases. RESULTS: In this study of 5200 ART and 20,800 naturally conceived (NC) control children, linear regression analysis revealed the birthweight of babies born from fresh embryo transfer cycles is 93.7 g [95% CI (76.6, 110.6)g] less than NC controls, whereas babies born from frozen embryo transfer (FET) cycles are 57.5 g [95% CI (30.7, 86.5)g] heavier. Fresh ART babies grew faster from birth (by 7.2 g/week) but remained lighter (by 171 g), at 6-8 weeks, than NC babies and 133 g smaller than FET babies; FET and NC babies were similar. Length and occipital-frontal circumference followed the same pattern. By school entry (4-7 years), weight, length and BMI in boys and girls conceived by fresh ART and FET were similar to those in NC children. CONCLUSIONS: ART babies born from fresh embryo transfer grow more slowly in utero and in the first few weeks of life, but then show postnatal catch up growth by school age, compared to NC and FET babies. As low birth weight and postnatal catch-up are independent risk factors for cardiometabolic disease over the life-course, we suggest that further studies in this area are now warranted.


Assuntos
Desenvolvimento Infantil , Transferência Embrionária/efeitos adversos , Transferência Embrionária/métodos , Peso ao Nascer , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Parto , Gravidez , Resultado da Gravidez , Fatores de Risco , Reino Unido
13.
J Infect Dis ; 218(7): 1099-1109, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-29733403

RESUMO

Background: The safety of iron supplementation for young women is uncertain in malaria-endemic settings. Methods: This was a double-blind, randomized controlled noninferiority trial in rural Burkina Faso. Results: A total of 1959 nulliparae were assigned to weekly supplementation (60 mg iron and 2.8 mg folic acid) (n = 980) or 2.8 mg folic acid (n = 979) until first antenatal visit (ANC1), or 18 months if remaining nonpregnant. Three hundred fifteen women attended ANC1, and 916 remained nonpregnant. There was no difference at ANC1 in parasitemia prevalence (iron, 53.4% [95% confidence interval {CI}, 45.7%-61.0%]; control, 55.3% [95% CI, 47.3%-62.9%]; prevalence ratio, 0.97 [95% CI, .79-1.18]; P = .82), anemia (adjusted effect, 0.96 [95% CI, .83-1.10]; P = .52), iron deficiency (adjusted risk ratio [aRR], 0.84 [95% CI, .46-1.54]; P = .58), or plasma iron biomarkers. Outcomes in nonpregnant women were parasitemia (iron, 42.9% [95% CI, 38.3%-47.5%]; control, 39.2% [95% CI, 34.9%-43.7%]; prevalence ratio, 1.09 [95% CI, .93-1.28]; P = .282); anemia (aRR, 0.90 [95% CI, .78-1.05]; P = .17), and iron deficiency (aRR, 0.99 [95% CI, .77-1.28]; P = .96), with no iron biomarker differences. Conclusions: Weekly iron supplementation did not increase malaria risk, improve iron status, or reduce anemia in young, mostly adolescent menstruating women, nor in early pregnancy. World Health Organization Guidelines for universal supplementation for young nulliparous women may need reassessment. Clinical Trials Registration: NCT01210040.


Assuntos
Anemia/prevenção & controle , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Ferro/administração & dosagem , Malária/prevenção & controle , Adolescente , Feminino , Humanos , Ferro/sangue , Gravidez , Organização Mundial da Saúde
14.
BMC Pregnancy Childbirth ; 18(1): 43, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29378526

RESUMO

BACKGROUND: Reducing stillbirth and early neonatal death is a national priority in the UK. Current evidence indicates this is potentially achievable through application of four key interventions within routine maternity care delivered as the National Health Service (NHS) England's Saving Babies' Lives care bundle. However, there is significant variation in the degree of implementation of the care bundle between and within maternity units and the effectiveness in reducing stillbirth and improving service delivery has not yet been evaluated. This study aims to evaluate the impact of implementing the care bundle on UK maternity services and perinatal outcomes. METHODS: The Saving Babies' Lives Project Impact and Results Evaluation (SPiRE) study is a multicentre evaluation of maternity care delivered through the Saving Babies' Lives care bundle using both quantitative and qualitative methodologies. The study will be conducted in twenty NHS Hospital Trusts and will include approximately 100,000 births. It involves participation by both service users and care providers. To determine the impact of the care bundle on pregnancy outcomes, birth data and other clinical measures will be extracted from maternity databases and case-note audit from before and after implementation. Additionally, this study will employ questionnaires with organisational leads and review clinical guidelines to assess how resources, leadership and governance may affect implementation in diverse hospital settings. The cost of implementing the care bundle, and the cost per stillbirth avoided, will also be estimated as part of a health economic analysis. The views and experiences of service users and service providers towards maternity care in relation to the care bundle will be also be sought using questionnaires. DISCUSSION: This protocol describes a pragmatic study design which is necessarily limited by the availability of data and limitations of timescales and funding. In particular there was no opportunity to prospectively gather pre-intervention data or design a phased implementation such as a stepped-wedge study. Nevertheless this study will provide useful practice-based evidence which will advance knowledge about the processes that underpin successful implementation of the care bundle so that it can be further developed and refined. TRIAL REGISTRATION: www.clinicaltrials.gov NCT03231007 (26th July 2017).


Assuntos
Implementação de Plano de Saúde/métodos , Serviços de Saúde Materna/estatística & dados numéricos , Programas Nacionais de Saúde/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde/métodos , Protocolos Clínicos , Feminino , Humanos , Recém-Nascido , Serviços de Saúde Materna/legislação & jurisprudência , Morte Perinatal/prevenção & controle , Gravidez , Pesquisa Qualitativa , Natimorto/epidemiologia , Reino Unido/epidemiologia
15.
Scientometrics ; 117(2): 745-769, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30595611

RESUMO

The global network of scientific collaboration created by researchers opens new opportunities for developing countries to engage in the process of knowledge creation historically lead by institutions in the developed world. The results discussed here explore how Cubans working in European science and technology might contribute to extending the scientific collaboration of the country through their ties with Cuban institutions mainly in the academic sector. A bibliometric method was used to explore the pattern of collaboration of Cuban researchers in Europe using the institutional affiliation of authors and collaborators. The records of scientific publications of the defined sample were obtained from Scopus database for the period between 1995 and 2014. The network of collaboration was generated using the affiliations of Cuban authors in Europe and co-authors with worldwide affiliations shown in the records of publications of each Cuban researcher of the study. The analysis of aggregate values of the output of Cuban researchers in Europe (1995-2014) reveals that their collaboration with Cuba correlates moderately with their performance in Europe. However, when taking into account their time publishing in Europe, the collaboration with Cuba decreases the longer they remain away from home. The network of collaborating Cuban researchers in Europe comprises 991 different affiliations from 58 countries: 698 from Europe, 118 from North America, 96 from Latin America and 79 from the rest of the world. K-core analysis of centrality shows two Cuban universities sharing the central position with another 24 institutions worldwide of which 18 belong to higher education.

16.
Eur J Cancer Care (Engl) ; 27(2): e12797, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29168588

RESUMO

This is a retrospective cohort study aiming to examine the response of oncology patients undergoing controlled ovarian stimulation (COS) for fertility preservation and to review the incidence of short-term complications. The study group consisted by all oncology patients undergoing ovarian stimulation for fertility preservation (n = 157) between April 2009 and April 2016. Patients undergoing COS for IVF/ICSI for male factor only infertility in the same time period (n = 2,128) provided a comparator group. Oncology patients underwent COS to retrieve eggs for storage and future use. The cancer patients had a very similar distribution of oocyte yield to the comparator group. Those with ovarian cancer did have significantly lower oocyte recovery than those with other cancers (age-adjusted difference 7, 95% CI: 2-12). None of the patients in the study group were admitted with ovarian hyperstimulation syndrome or any other complication of COS or oocyte retrieval. This is one of the largest reported cohorts of patients treated for fertility preservation before oncology treatment. Our data have demonstrated a good response to stimulation, offering a reasonable chance of pregnancy in the future. In contrast to previous studies, we have demonstrated a similar number of oocytes retrieved to that of women undergoing IVF/ICSI treatment for male factor infertility.


Assuntos
Preservação da Fertilidade/métodos , Infertilidade Feminina/prevenção & controle , Neoplasias/complicações , Indução da Ovulação , Adulto , Feminino , Hormônio Foliculoestimulante/uso terapêutico , Humanos , Recuperação de Oócitos/normas , Gravidez , Estudos Retrospectivos
17.
Matern Child Nutr ; 14(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28421711

RESUMO

The prevalence of vitamin D deficiency in pregnant white-skinned women (WSW) and their infants has not been investigated at northern latitudes in a developed county. A 2-year observational cohort study was undertaken in the North West of England to determine 25-hydroxyvitamin D (25OHD) levels in WSW and their infants during pregnancy and 4 months postdelivery and to explore factors associated with these levels. Nutritional and lifestyle questionnaires were completed and 25OHD levels measured at 28 weeks and 4 months postdelivery. Twenty-seven percent and 7% of WSW had insufficient and deficient levels of 25OHD during pregnancy and 48% and 11% four months postdelivery. WSW with Fitzpatrick skin-type I (FST I) have significantly lower 25OHD than other skin types after controlling for time spent outside and vitamin D intake. Twenty-four percent and 13% of infants had insufficient and deficient 25OHD levels at 4 months. Unsupplemented breast-fed infants have the highest level of insufficiency (67%) compared with formula-fed infants (2%). Factors associated with infant serum 25OHD levels at 4 months included breast feeding, supplementation, and time outside. WSW have a high prevalence of insufficiency and deficiency during pregnancy which doubles 4 months after birth. Breast-fed infants of WSW are rarely considered at risk of vitamin D insufficiency but have high rates compared with formula-fed infants. This is the first study to show the finding that FST I WSW have significantly lower levels of 25OHD than those with FST II-IV (difference adjusted for diet and time outside 14 (95%CI 7-21) nmol/L).


Assuntos
Dieta , Grupo com Ancestrais do Continente Europeu , Estado Nutricional , Deficiência de Vitamina D/epidemiologia , Adulto , Aleitamento Materno , Estudos de Coortes , Suplementos Nutricionais , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Período Pós-Parto , Gravidez , Estações do Ano , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue
18.
BMC Med ; 15(1): 206, 2017 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-29166928

RESUMO

BACKGROUND: Provision of routine iron supplements to prevent anaemia could increase the risk for lower genital tract infections as virulence of some pathogens depends on iron availability. This trial in Burkina Faso assessed whether weekly periconceptional iron supplementation increased the risk of lower genital tract infection in young non-pregnant and pregnant women. METHODS: Genital tract infections were assessed within a double blind, controlled, non-inferiority trial of malaria risk among nulliparous women, randomised to receive either iron and folic acid or folic acid alone, weekly, under direct observation for 18 months. Women conceiving during this period entered the pregnancy cohort. End assessment (FIN) for women remaining non-pregnant was at 18 months. For the pregnancy cohort, end assessment was at the first scheduled antenatal visit (ANC1). Infection markers included Nugent scores for abnormal flora and bacterial vaginosis (BV), T. vaginalis PCR, vaginal microbiota, reported signs and symptoms, and antibiotic and anti-fungal prescriptions. Iron biomarkers were assessed at baseline, FIN and ANC1. Analysis compared outcomes by intention to treat and in iron replete/deficient categories. RESULTS: A total of 1954 women (mean 16.8 years) were followed and 478 (24.5%) became pregnant. Median supplement adherence was 79% (IQR 59-90%). Baseline BV prevalence was 12.3%. At FIN and ANC1 prevalence was 12.8% and 7.0%, respectively (P < 0.011). T. vaginalis prevalence was 4.9% at FIN and 12.9% at ANC1 (P < 0.001). BV and T. vaginalis prevalence and microbiota profiles did not differ at trial end-points. Iron-supplemented non-pregnant women received more antibiotic treatments for non-genital infections (P = 0.014; mainly gastrointestinal infections (P = 0.005), anti-fungal treatments for genital infections (P = 0.014) and analgesics (P = 0.008). Weekly iron did not significantly reduce iron deficiency prevalence. At baseline, iron-deficient women were more likely to have normal vaginal flora (P = 0.016). CONCLUSIONS: Periconceptional weekly iron supplementation of young women did not increase the risk of lower genital tract infections but did increase general morbidity in the non-pregnant cohort. Unabsorbed gut iron due to malaria could induce enteric infections, accounting for the increased administration of antibiotics and antifungals in the iron-supplemented arm. This finding reinforces concerns about routine iron supplementation in highly malarious areas. TRIAL REGISTRATION: Trial registration number NCT01210040 . Registered with Clinicaltrials.gov on 27 September 2010.


Assuntos
Ácido Fólico/farmacologia , Ferro/farmacologia , Infecções do Sistema Genital/induzido quimicamente , Adolescente , Anemia/prevenção & controle , Burkina Faso , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Ácido Fólico/administração & dosagem , Seguimentos , Humanos , Malária/diagnóstico , Gravidez , Cuidado Pré-Natal , Prevalência , Vagina/microbiologia
20.
Genet Med ; 19(9): 1032-1039, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28301457

RESUMO

PURPOSE: Broadening access to genomic testing and counseling will be necessary to realize the benefits of personalized health care. This study aimed to assess the feasibility of delivering a standardized genomic care model for inherited retinal dystrophy (IRD) and of using selected measures to quantify its impact on patients. METHODS: A pre-/post- prospective cohort study recruited 98 patients affected by IRD to receive standardized multidisciplinary care. A checklist was used to assess the fidelity of the care process. Three patient-reported outcome measures-the Genetic Counselling Outcome Scale (GCOS-24), the ICEpop CAPability measure for Adults (ICECAP-A), and the EuroQol 5-dimension questionnaire (EQ-5D)-and a resource-use questionnaire were administered to investigate rates of missingness, ceiling effects, and changes over time. RESULTS: The care model was delivered consistently. Higher rates of missingness were found for the genetic-specific measure (GCOS-24). Considerable ceiling effects were observed for the generic measure (EQ-5D). The ICECAP-A yielded less missing data without significant ceiling effects. It was feasible to use telephone interviews for follow-up data collection. CONCLUSION: The study highlighted challenges and solutions associated with efforts to standardize genomic care for IRD. The study identified appropriate methods for a future definitive study to assess the clinical effectiveness and cost-effectiveness of the care model.Genet Med advance online publication 02 March 2017.


Assuntos
Assistência à Saúde , Genômica , Oftalmologia , Padrão de Cuidado , Algoritmos , Estudos de Coortes , Assistência à Saúde/métodos , Assistência à Saúde/normas , Gerenciamento Clínico , Feminino , Aconselhamento Genético , Testes Genéticos/métodos , Testes Genéticos/normas , Genômica/métodos , Humanos , Masculino , Modelos Teóricos , Oftalmologia/métodos , Oftalmologia/normas , Aceitação pelo Paciente de Cuidados de Saúde , Medidas de Resultados Relatados pelo Paciente , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética
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