Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease.

BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10-15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

Clonidine vs. midazolam as premedication in children undergoing adeno-tonsillectomy: a prospective, randomized, controlled clinical trial.

BACKGROUND: Clonidine administration in the setting of paediatric anaesthesia is associated with a number of desirable effects, e.g. preoperative sedation, analgesia and reduced anaesthetic requirements. The aim of the current study was to compare postoperative outcome variables using a prospective, randomized, double-blind design after premedication with clonidine or midazolam. METHODS: One hundred paediatric ASA physical status 1 patients (age 1-11 year) scheduled for adeno-tonsillectomy were assigned to receive rectal premedication with midazolam (300 microg kg(-1) and atropine 40 microg kg(-1); group M, n = 52) or clonidine (5 microg kg(-1 and) atropine 40 microg kg(-1); group C, n = 48) prior to a standardized sevoflurane anaesthetic. The incidence of immediate postoperative pain (0-2 h), as assessed by repeated Objective Pain Scale (OPS) scores, was chosen as the primary end-point of the study. Degree of sedation (modified Vancouver sedation scale 0-3), occurrence of postoperative vomiting (POV), and incidence of shivering and immediate postoperative confusion were registered as secondary end-points. After hospital discharge parents were instructed to continue the evaluation of pain, sedation, POV and sleep pattern during a 24-h period. Parents were also asked for their preference concerning the postoperative behaviour of their child (calm, sedated vs. alert, active). RESULTS: In the early postoperative period patients in the clonidine group had a significantly lower sum of 5 OPS scores (median = 8.0) compared to group M (median = 11.5) (P = 0.011). Administration of clonidine was also associated with a slightly higher sum of sedation scores (median = 13) in the early postoperative period compared to children receiving midazolam (median = 12) (P < 0.001). No episode of shivering was observed in the clonidine group but was present in five of the patients in the midazolam group (P = 0.057). In younger children (< 5 years) the incidence of postoperative confusion was lower in the clonidine group (P = 0.001). No difference in the frequencies of POV incidences, degree of postoperative pain, need for analgesics, or sleep pattern during the first 24 postoperative hours could be observed between the groups according to the parental evaluation. Children premedicated with clonidine were more calm and sedated compared to children in the midazolam group (P = 0.024) as judged by their parents. A significant majority of parents (75%; P < 0.001) preferred a calm and sedated child during the first postoperative 24-h period. CONCLUSION: Rectal premedication with clonidine was associated with a significant reduction of pain in the early postoperative period compared to midazolam and was also associated with moderately increased sedation during the first 24 postoperative hours. The sedative effect of clonidine is in agreement with the unambiguous finding of a parental preference for a calm and sedated child during the first 24 postoperative hours.

Snowmobile injuries in Kiruna, northern Sweden.

Snowmobile injury events in Kiruna, northern Sweden, have been studied over a 3-year period. The area is large and fairly isolated with centrally located health facilities which provides a study population that reflects the actual incidence of injury events in the area. It is also a region with an extremely frequent use of snowmobiles. A series of 109 persons injured in snowmobiling crashes were analysed. The number of injury events per registered vehicles was 5/1000. There were 88 males and 21 females with the peak injury frequency in the age group 20-29 years. Six persons were under the age of 16. Most of the patients were drivers and the most common accident mechanism was falling off the machine and sudden stops. The total number of injuries were 1.1/patient. The lower extremities were the most commonly injured sites (32%). In 26% of the cases there were non-minor injuries. Nineteen patients needed in-patient care with a mean duration of hospital stay of 5.7 days. We also report four fatalities that occurred during the time of the study.

Prevalence of protein-energy malnutrition in a large population of elderly people at home.

The prevalence of protein-energy malnutrition (PEM) was examined in 1206 randomly selected elderly people aged 65 to 80 years living in their own homes. Nutritional assessment was based on weight loss, weight index, triceps skin fold, arm muscle circumference, serum albumin and prealbumin, and delayed cutaneous hypersensitivity (DCH) reaction. The prevalence of PEM was 5 per cent. If people with signs of inflammation were excluded, the prevalence of PEM was 3.5 per cent. When other nutritional indices, used by other authors among hospitalized patients, were applied to our sample prevalence values from 2.6 to 4.1 per cent were obtained. the prevalence was not related to sex or age. DCH increased the sensitivity of the screening method but causes of anergy other than PEM must be taken into account. It is concluded that PEM, in a degree shown to impair the prognosis at hospital, does occur among elderly people at home in an industrialized country.

Skin blood flow in an area at risk for pressure sore.

The aim of this study was to measure skin blood flow in patients with pressure sore in a long-term care unit. For comparison, measurements were also carried out on in-patients at risk of developing pressure sores and on healthy individuals in the same age groups as the in-patients. Skin blood flow was measured in the morning, using a laser-Doppler flowmeter. Measurements were made over the lateral part of the hip and over the lateral part of the upper arm. Measurements were carried out first at ambient temperature. The flow was then followed as the local skin region was heated to 40 degrees C. The results indicate that in healthy individuals the heat stimulus increased skin blood flow over the lateral part of the hip more than in in-patients in the same age group. Individuals below the age of 60 have a greater response than those over the age of 60. This impairment in the ability of the older in-patients to increase skin blood flow in response to thermal stimulus may be a factor in the development of pressure sores.

Delayed hypersensitivity. A critical evaluation of five recall antigens in a large reference population.

The reactivity to five recall antigens, candida, mumps, PPD, varidase and trichophyton and the corresponding diluents was tested in 840 healthy persons aged between 17 and 101 years. Candida antigen was tested in a lower (l) and a higher (h) dose. The size of reactions did not follow a Gaussian distribution and we therefore used the 10th and 5th percentiles instead of standard deviation to define the limits between positive, weak and negative reactions. The number of positive reactions to each of candida-h, mumps, PPD and varidase was between 80 and 95 per cent in patients less than 60 years of age and above this age it varied between 0 and 85 per cent. The number of positive reactions to candida-l and trichophytin was low in all ages. The reactivity was regarded as normal if there was a positive reaction i.e.sum of right angle diameters >10 mm to atl east one antigen, relatively anergic if there was only a weak reaction (7-9 mm) and anergic if there was a negative reaction (0-6 mm) to all antigens. A normal reaction was found in 100 per cent of subjects up to 60 years of age, and in 95 per cent up to 30 years. Among those with normal reactivity, positive results were found with candida-h alone in between 67-93 per cent, candida-h + mumps between 92-100 per cent and candida + mumps + PPD in 100 per cent irrespective of age.

Vitamin D deficiency in welfare institutions for the aged.

Serum concentrations of 25-OH-D in a group of 47 elderly people (70--94 years old) living in homes for the aged were lower than those in a matched control group living in their homes. No differences between the groups were noted in serum ionized calcium, alkaline phosphatase, inorganic phosphate, magnesium or parathyroid hormone. The low serum concentration of 25-OH-D may be due to less outdoor activities and/or a smaller dietary vitamin D intake in the institutionalized group. The importance of preserving an adequate vitamin D status in geriatric patients is emphasized.