A genome-wide linkage study in families with major depression and co-morbid unexplained swelling.

Major depressive disorder (MDD) is a common heritable condition. The diversity of the phenotype coupled with aetiological and genetic heterogeneity present formidable obstacles in the search for causative genetic loci. Studies of large families with many affected individuals, and the selection of well-defined clinical subgroups of depression, are two ways to reduce this complexity. Unexplained swelling symptoms (USS) are common in women and many patients give a strong personal and family history of depression. Co-morbid depression and swelling symptoms define a useful sub-phenotype for investigating genetic factors in depression. We have completed a genome-wide linkage analysis using 371 microsatellite markers in four families where MDD is co-morbid with USS. Of 47 affected individuals, 28 had both MDD and unexplained swelling, 11 had symptoms of swelling alone, and 8 had MDD alone. Parametric marker-specific analysis identified one suggestive locus, D8S260 (LOD = 2.02) and non-parametric multipoint variance component analysis identified a region on 7p (LOD = 2.10). A 47 cM suggestive linkage region on chromosome 14q (identified by both parametric and non-parametric methods) was identified and investigated further with fine-mapping markers but the evidence for linkage to this region decreased with increased marker information content.

Meat consumption reduces the risk of nutritional rickets and osteomalacia.

Endogenous vitamin D deficiency (low serum 25(OH)D3) is a necessary but insufficient requirement for the genesis of vitamin D-deficiency rickets and osteomalacia. The magnitude of the independent contributions of dietary factors to rachitic and osteomalacic risk remains uncertain. We reanalysed two weighed dietary surveys of sixty-two cases of rickets and osteomalacia and 113 normal women and children. The independent associations of four dietary variables (vitamin D, Ca, fibre and meat intakes) and daylight outdoor exposure with rachitic and osteomalacic relative risk were estimated by multivariate logistic regression. Meat and fibre intakes showed significant negative and positive associations respectively with rachitic and osteomalacic relative risk (RR; zero meat intake: RR 29.8 (95 % CI 4.96, 181), P<0.001; fibre intake: RR 1.53 (95 % CI 1.01, 2.32), P=0.043). The negative association of meat intakes with rachitic and osteomalacic relative risk was curvilinear; relative risk did not fall further at meat intakes above 60 g daily. Daylight outdoor exposure showed a significant negative association with combined relative risk (RR 0.33 (95 % CI 0.17, 0.66), P<0.001). Operation of the meat and fibre risk factors was related to sex, age and dietary pattern (omnivore/lactovegetarian), mainly determined by religious affiliation. The mechanism by which meat reduces rachitic and osteomalacic risk is uncertain and appears independent of revised estimates of meat vitamin D content. The meat content of the omnivore Western diet may explain its high degree of protection against nutritional rickets and osteomalacia from infancy to old age in the presence of endogenous vitamin D deficiency.

Downsizing of acute inpatient beds associated with private finance initiative: Scotland's case study.

OBJECTIVES: To evaluate whether the projected 24% reduction in acute bed numbers in Lothian hospitals, which formed part of the private finance initiative (PFI) plans for the replacement Royal Infirmary of Edinburgh, is being compensated for by improvements in efficiency and greater use of community facilities, and to ascertain whether there is an independent PFI effect by comparing clinical activity and performance in acute specialties in Lothian hospitals with other NHS hospitals in Scotland. DESIGN: Comparison of projected and actual trends in acute bed capacity and inpatient and day case admissions in the first five years (1995-6 to 2000-1) of Lothian Health Board's integrated healthcare plan. Population study of trends in bed rate, hospital activity, length of stay, and throughput in Lothian hospitals compared with the rest of Scotland from 1990-1 to 2000-1. MAIN OUTCOME MEASURES: Staffed bed rates, admission rates, mean lengths of stay, occupancy, and throughput in four adult acute specialty groups in 1990-1, 1995-6, and 2000-1. RESULTS: By 2000-1, rates for inpatient admission in all acute, medical, surgical, and intensive therapy specialties in Lothian hospitals were respectively 20%, 6%, 28%, and 38% below those in the rest of Scotland. Day case rates in all acute and acute surgical specialties were 13% and 33% lower. The proportion of delayed discharges in staffed acute and post-acute NHS beds in Lothian hospitals exceeded the Scottish average (15% and 12% respectively; P<0.001). CONCLUSION: The planning targets and increase in clinical activity in acute specialties in Lothian hospitals associated with PFI had not been achieved by 2000-1. The effect on clinical activity has been a steeper decline in the number of acute beds and rates of admission in Lothian hospitals compared with the rest of Scotland between 1995-6 and 2000-1.