A national register for surveillance of inherited disorders: beta thalassaemia in the United Kingdom

OBJECTIVE: To demonstrate the value of a national register for surveillance of services for an inherited disorder. METHODS: Data from the United Kingdom Thalassaemia Register and the United Kingdom Register of Prenatal Diagnosis for Haemoglobin Disorders were combined in a database; these registers include all fetuses known to have been diagnosed with beta thalassaemia major, beta thalassaemia intermedia, or haemoglobin E/beta thalassaemia in the United Kingdom. Data were extracted to show outcomes (selective abortion or live birth) of all fetuses and the status of those born with a disorder (alive, dead, successful bone marrow transplant, or lost to follow-up) by parents' region of residence and ethnicity. FINDINGS: At the end of 1999 the register included 1074 patients, 807 of whom were alive and residing in the United Kingdom. A successful bone marrow transplant has been performed for 117 out of 581 (20%) patients born since 1975. Residents of Pakistani origin are now the main group at risk in the United Kingdom, replacing residents of Cypriot origin. This has led to a marked shift in the need for services from the south-east of England to the Midlands and the north of England. Despite the acceptability of prenatal diagnosis, the proportion of affected births remains 50% higher than would be expected, reflecting a widespread failure to deliver timely screening and counselling to carriers. Even though effective treatment is available the annual number of deaths is rising, indicating that better tolerated treatments are needed. CONCLUSION: A national diagnosis register is a powerful instrument for monitoring the treatment and prevention of inherited disorders and for highlighting correctable shortcomings. In view of the increasing possibilities for genetic screening there is a strong case for central funding for such databases within modern health services

The Economic Resource Receipt of New Mothers

U.S. federal policies do not provide a universal social safety net of economic support for women during pregnancy or the immediate postpartum period but assume that employment and/or marriage will protect families from poverty. Yet even mothers with considerable human and marital capital may experience disruptions in employment, earnings, and family socioeconomic status postbirth. We use the National Survey of Families and Households to examine the economic resources that mothers with children ages 2 and younger receive postbirth, including employment, spouses, extended family and social network support, and public assistance. Results show that many new mothers receive resources postbirth. Marriage or postbirth employment does not protect new mothers and their families from poverty, but education, race, and the receipt of economic supports from social networks do

Estimating the birth prevalence and pregnancy outcomes of congenital malformations worldwide

Congenital anomaly registries have two main surveillance aims: firstly to define baseline epidemiology of important congenital anomalies to facilitate programme, policy and resource planning, and secondly to identify clusters of cases and any other epidemiological changes that could give early warning of environmental or infectious hazards. However, setting up a sustainable registry and surveillance system is resource-intensive requiring national infrastructure for recording all cases and diagnostic facilities to identify those malformations that that are not externally visible. Consequently, not all countries have yet established robust surveillance systems. For these countries, methods are needed to generate estimates of prevalence of these disorders which can act as a starting point for assessing disease burden and service implications. Here, we describe how registry data from high-income settings can be used for generating reference rates that can be used as provisional estimates for countries with little or no observational data on non-syndromic congenital malformations

Methods to estimate access to care and the effect of interventions on the outcomes of congenital disorders

In the absence of intervention, early-onset congenital disorders lead to pregnancy loss, early death, or disability. Currently, lack of epidemiological data from many settings limits the understanding of the burden of these conditions, thus impeding health planning, policy-making, and commensurate resource allocation. The Modell Global Database of Congenital Disorders (MGDb) seeks to meet this need by combining general biological principles with observational and demographic data, to generate estimates of the burden of congenital disorders. A range of interventions along the life course can modify adverse outcomes associated with congenital disorders. Hence, access to and quality of services available for the prevention and care of congenital disorders affects both their birth prevalence and the outcomes for affected individuals. Information on this is therefore important to enable burden estimates for settings with limited observational data, but is lacking from many settings. This paper, the third in this special issue on methods used in the MGDb for estimating the global burden of congenital disorders, describes key interventions that impact on outcomes of congenital disorders and methods used to estimate their coverage where empirical data are not available

Primary care morbidity in Eastern Cape Province

Background. Primary health care in rural South Africa is predominantly provided by remote clinics and health centres. In 1994, health centres were upgraded and new health centres developed to serve as a health care filter between community clinics and district hospitals.Aim. To describe the spectrum of clinical problems encountered at a new health centre in an area of high economic deprivation and compare this with an adjacent community clinic and district hospital.Design. Cross-sectional survey.Setting. A rural clinic, health centre and district hospital in Eastern Cape Province, South Africa.Methods. The International Classification of Primary Care-2(ICPC-2) was used to code data collected over a 13-week period from patients presenting at a community clinic, health centre and district hospital.Results. Altogether, 4 383 patient encounters were recorded across all three sites. Most contacts at the clinic (97%) and the health centre (80%) were with a nurse. Females over 15 years of age comprised over half of all contacts at health facilities (53%). The most common diagnosis category was respiratory (23%). Cough was the most common symptom.Thirty per cent of children up to 5 years of age were seen for immunisations. Most childhood immunisations (79%) werecarried out at the health centre.Conclusion. Of all the health care facilities surveyed, the health centre had the highest throughput of patients, indicating that the health centre is an efficient filter between the community and hospital. The ICPC-2 can be successfully used to monitor encounters at similar African health care facilities.S Afr Med J 2010; 100: 309-312

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies

Interstellar MHD Turbulence and Star Formation

This chapter reviews the nature of turbulence in the Galactic interstellar medium (ISM) and its connections to the star formation (SF) process. The ISM is turbulent, magnetized, self-gravitating, and is subject to heating and cooling processes that control its thermodynamic behavior. The turbulence in the warm and hot ionized components of the ISM appears to be trans- or subsonic, and thus to behave nearly incompressibly. However, the neutral warm and cold components are highly compressible, as a consequence of both thermal instability in the atomic gas and of moderately-to-strongly supersonic motions in the roughly isothermal cold atomic and molecular components. Within this context, we discuss: i) the production and statistical distribution of turbulent density fluctuations in both isothermal and polytropic media; ii) the nature of the clumps produced by thermal instability, noting that, contrary to classical ideas, they in general accrete mass from their environment; iii) the density-magnetic field correlation (or lack thereof) in turbulent density fluctuations, as a consequence of the superposition of the different wave modes in the turbulent flow; iv) the evolution of the mass-to-magnetic flux ratio (MFR) in density fluctuations as they are built up by dynamic compressions; v) the formation of cold, dense clouds aided by thermal instability; vi) the expectation that star-forming molecular clouds are likely to be undergoing global gravitational contraction, rather than being near equilibrium, and vii) the regulation of the star formation rate (SFR) in such gravitationally contracting clouds by stellar feedback which, rather than keeping the clouds from collapsing, evaporates and diperses them while they collapse.Comment: 43 pages. Invited chapter for the book "Magnetic Fields in Diffuse Media", edited by Elisabete de Gouveia dal Pino and Alex Lazarian. Revised as per referee's recommendation

Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis

Currently there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, first, that family networks hold strong potential for cascading genetic information, making the adoption of a family centred approach an efficient strategy for this community. However, this is dependent on provision of high quality and timely information from health care providers. Secondly, families’ experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals’ views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information