Developing and validating models for predicting nursing home admission using only RAI-HC instrument data.

OBJECTIVE: In recent years research has identified important predictors for nursing home admission (NHA). However, as far as we know, the previous risk models use complex variable sets from many sources and the output is a single risk value. The objective of this study was to develop an NHA risk model with a variable set from single data source and richer output information. METHODS: In this study, we developed a model selecting variables only from the RAI-HC (Resident Assessment Instrument - Home Care) system. Furthermore, we used principal component analysis and K-means clustering to target proper interventions for high-risk clients. RESULTS: The performance of the model was close to the complex previous model (recall [Formula: see text] vs. [Formula: see text] and specificity [Formula: see text] vs. [Formula: see text]). For the risk clients, three intervention clusters (deficiency in physical functionality, deficiency in cognitive functionality and depression and mood disorders) were found. CONCLUSION: The NHA risk model and intervention clusters are important because they enable the identification of proper interventions for the right clients. The fact that the model with RAI-HC data alone was accurate enough simplifies the integration of the NHA risk model into practice because it uses data from one system and the algorithm can be integrated easily into the source system.

HLA associations with tubulointerstitial nephritis with or without uveitis in Finnish pediatric population: a nation-wide study.

The human leukocyte antigen (HLA) genotype has been shown to associate with tubulointerstitial nephritis (TIN) and tubulointerstitial nephritis with uveitis syndrome (TINU). The association of HLA genes with TIN was examined in this nation-wide study. HLA genotyping was performed in 31 pediatric patients with biopsy-proven TIN. All patients were examined by an ophthalmologist to diagnose possible uveitis. Class II HLA genotypes of TIN patients were compared with the Finnish reference population. We found a significant association between the HLA alleles DQA1*04:01 [risk ratio (RR) 5.0, 95% confidence interval (CI) 2.0-11.2], DQB1*04:02 (RR 2.7, 95% CI 1.4-5.3), and DRB1*08 (RR 3.8, 95% CI 1.5-8.4) and TIN. Uveitis was found in 20/31 (64.5%) patients. HLA genotyping of the TINU patients showed additional risk HLA alleles: DQA1*01:04 (RR 6.1, 95% CI 1.5-17.8), and DRB1*14 (RR 8.2, 95% CI 2.2-22.1). The alleles DQA1*01:04 (RR 8.8, 95% CI 2.2-26.5), DQA1*04:01 (RR 3.2, 95% CI 1.2-7.3), and DRB1*14 (RR 12.0, 95% CI 3.2-33.0) were more frequent in patients with TIN and chronic uveitis than in reference population. The HLA class II haplotype DQA1*04:01/DQB1:04:02/DRB1*08 was the most common combination in our study population (58.1%). None of the patients had haplotype DQA1*04:01/DQB1*06:02/DRB1*15, which is common in Finland. HLA genotype did not predict the renal outcome. We found a strong association between certain HLA genotypes both in TIN and TINU patients. The TIN/TINU-associated HLA alleles appear to vary depending on study population.

Outcome of Henoch-Schoenlein nephritis with nephrotic-range proteinuria.

PATIENTS AND METHODS: All children with Henoch-Schoenlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria (> 40 mg/h/m2), treated at 5 university hospitals and in 1 central hospital in Finland during in 1990-1997, were analyzed retrospectively. The mean age of these 19 patients (8 girls, 11 boys) at the time of diagnosis was 9.9 years (range 4.6-15.1 years). A renal biopsy had been performed in all cases, giving findings according to the classification used in the International Study of Kidney Diseases in Children (ISKDC) of grade II (4 patients), grade III (10), grade IV (4) and grade V (1). Six patients underwent a second biopsy. RESULTS: The yearly incidence of nephrotic-range HSP-GN in Finland was 2 per 1 million children under 15 years of age. After a mean follow-up of 4.6 years (range 9 months-9.1 years), 3 patients (15.7%) had no signs of nephritis, 11 (57.9%) had proteinuria < 1 g/day or microscopic hematuria, 2 (10.5%) had proteinuria > 1 g/day, and 3 (15.7%) had developed ESRD or uremia. 47% of the patients needed medication for proteinuria at the time of the latest follow-up. The first kidney biopsy did not predict the outcome of HSP-GN, since all the patients with the poorest outcome had only ISKDC II-III findings in their first biopsy. CONCLUSION: According to our series, the morbidity in cases of HSP-GN with nephrotic-range proteinuria is high and a close clinical follow-up is needed. The treatment of HSP-GN patients should be based on the clinical presentation rather than on the biopsy findings.

Comparison of cyclosporin and UVAB phototherapy for intermittent one-year treatment of atopic dermatitis.

Although cyclosporin is effective for the treatment of severe atopic dermatitis, phototherapy is the standard second-line treatment for this disease. An open, randomized, controlled, parallel-group study was conducted to compare the efficacy, influence on quality of life and safety of cyclosporin and UVAB phototherapy during 1 year of intermittent treatment of atopic dermatitis in adult patients. The main endpoints of the study were the number of days in remission and the influence on quality of life. Seventy-two patients were treated, 36 in each group. Cyclosporin produced significantly more days in remission than UVAB phototherapy during the 1-year study period. At the end of the study no difference between the 2 groups was noted in terms of quality of life. A significant increase in serum creatinine occurred in 2 patients and 7 patients developed mild or moderate hypertension during cyclosporin treatment. It can be concluded that intermittent cyclosporin seems to be more effective than UVAB and is reasonably safe for the treatment of atopic dermatitis over a 1-year treatment period.

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women.

OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. DESIGN: Open, randomised controlled 12 month follow up trial. SETTING: Health centres for university students and staff of university hospital. PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. INTERVENTIONS: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. MAIN OUTCOME MEASURE: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen. RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.

A pessimistic attitude towards the future and low psychosocial functioning predict psychiatric diagnosis among treatment-seeking adolescents.

OBJECTIVE: The objective was to study factors associated with psychiatric diagnosis among adolescents (n = 164) seeking psychiatric care for mental symptoms. METHOD: Psychiatric diagnosis was confirmed by a structured diagnostic interview. Psychosocial functioning was assessed with the Global Assessment of Functioning Scale, and the Beck Depression Inventory and Offer Self-Image Questionnaire were also used. Background data were gathered. RESULTS: A majority (76%) of the adolescents met DSM-III-R criteria for psychiatric diagnosis. The self-image was more negative and the Beck score was higher among these adolescents than the others. All who had attempted suicide had a psychiatric disorder. Those diagnosed as having a psychiatric disorder consumed alcohol in order to get drunk more often than others. Continual conflicts with parents and smoking were not associated with the existence of a psychiatric disorder. In logistic regression analysis, low psychosocial functioning (OR = 3.9) and an uncertain or pessimistic attitude towards the future (OR = 9.1) proved to be independent risk factors for psychiatric disorders. CONCLUSIONS: Health service staff should be aware of factors associated with psychiatric disorders in adolescents so that they can identify those at high risk.

Recurrence and follow-up after urinary tract infection under the age of 1 year.

In order to analyze the risk factors for recurrence and the value of routine follow-up by monthly urine cultures in a group of children who had their first episode of urinary tract infection (UTI) under 1 year of age, we performed a retrospective survey of 262 children (134 girls, 128 boys) who were treated for their first UTI while aged under 1 year in the Department of Pediatrics, University of Oulu, during the years 1978-1984. Detailed data on these children concerning their first and recurrent UTIs were collected from hospital records using a formulated data sheet. Causative bacteria and vesicoureteral reflux (VUR) were analyzed as possible risk factors for recurrent UTI. The time of recurrence and the possible symptoms during the recurrent UTI were also investigated. The follow-up period after the first UTI was 3 years; 35% of the boys and 32% of the girls contracted a recurrent UTI during the 3-year follow-up. In 86% of cases, the first UTI recurrence occurred within 6 months of the primary UTI. Recurrent UTIs were detected significantly earlier with routine monthly follow-up compared with those seeking treatment because of symptoms (log rank test P < 0.01). There was a significant difference in the number of recurrences of UTI according to the grade of VUR (P = 0.006). Recurrence-free survival was shorter and recurrent UTIs occurred more often in the children with grade 3-5 VUR than in those with grade 0-2 VUR (log rank test P = 0.0005). Children without VUR and children with grade 1-2 VUR did not differ in the recurrence rate, and thus grade 1-2 VUR did not increase the risk for recurrent UTI. Monthly routine urine cultures are efficient in detecting recurrent UTI infections in children. Since grade 3-5 VUR is a risk factor both for increased recurrence rate of UTI and for possible subsequent renal damage, these children should be followed with monthly urine cultures for UTI recurrences if not on preventive medication. Since the vast majority of UTI recurrences occur within 6 months of the first UTI, routine follow-up for 6 months seems to be sufficient after symptomatic UTI in children with grade 3-5 VUR.

Nephrectomy in severe hypertension.

We describe a 12-year-old girl who died due to hypertensive encephalopathy and a 7-year-old boy with a favorable outcome after bilateral nephrectomy. Both had end-stage renal disease. Nephrectomy should be considered as a possible treatment of severe hypertension even without end-stage renal disease, if the patient has symptoms of hypertensive encephalopathy.

Childhood encephalopathies and myopathies: a prospective study in a defined population to assess the frequency of mitochondrial disorders.

OBJECTIVES: To assess the frequency of mitochondrial abnormalities in muscle histology, defects in respiratory chain enzyme activities, and mutations in mitochondrial DNA (mtDNA) in children with unexplained psychomotor retardation in the population of Northern Finland. BACKGROUND: The frequency of mitochondrial diseases among patients with childhood encephalopathies and myopathies is not known. Frequencies are difficult to estimate because the clinical presentation of these disorders is variable. METHODS: A total of 116 consecutive patients with undefined encephalopathies and myopathies were enrolled during a 7-year period in a hospital serving as the only neurologic unit for a pediatric population of 97 609 and as the only tertiary level neurologic unit for a pediatric population of 48 873. Biochemical and morphologic investigations were performed on muscle biopsy material, including oximetric and spectrophotometric analyses of oxidative phosphorylation, histochemistry, electron microscopy, and molecular analysis of mtDNA. RESULTS: Ultrastructural changes in the mitochondria were the most common finding in the muscle biopsies (71%). Ragged-red fibers were found in 4 cases. An oxidative phosphorylation defect was found in 26 children (28%), complex I (n = 15) and complex IV (n = 13) defects being the most common. Fifteen percent of patients (n = 17/116) with unexplained encephalomyopathy or myopathy had a probable mitochondrial disease. Common pathogenic mutations were found in the mtDNA of only 1 patient (.9%). CONCLUSIONS: The common known mutations in mtDNA are rarely causes of childhood encephalomyopathies, which is in contrast to the considerable frequency of the common MELAS mutation observed among adults in the same geographical area. Biochemically and morphologically verified mitochondrial disorders were nevertheless common among the children, making the analysis of a muscle biopsy very important for clinical diagnostic purposes.

A double-blind, randomized study to compare the efficacy and safety of terbinafine (Lamisil) with fluconazole (Diflucan) in the treatment of onychomycosis.

In a randomized, double-blind, double-placebo, multicentre study, terbinafine 250 mg daily for 12 weeks was compared with fluconazole 150 mg once weekly for 12 or 24 weeks in the treatment of onychomycosis. A total of 137 patients with culture-confirmed onychomycosis was divided into three groups: group A received terbinafine for 12 weeks, group B received fluconazole for 12 weeks, while group C received fluconazole for 24 weeks. At completion of the study (week 60), the mycological cure rate was higher in the terbinafine group than in the fluconazole groups: 89% vs. 51% and 49%, respectively (P < 0.001). The length of unaffected nail increased until week 24 in group B and until week 36 in group C, but was still increasing in group A at the final visit (week 60). Complete clinical cure of the target nail at week 60 was 67% in the terbinafine group, compared with 21% and 32% in the fluconazole groups, respectively. The incidence of adverse events was low for both study agents. We conclude that terbinafine 250 mg daily for 12 weeks is significantly more effective in the treatment of onychomycosis than fluconazole 150 mg once weekly for either 12 or 24 weeks.

Angiotensin converting enzyme gene insertion/deletion polymorphism, angiotensinogen gene polymorphisms, family history of hypertension, and childhood blood pressure.

Earlier epidemiologic studies have yielded inconsistent results on the extent and timing of the blood pressure (BP) increase in offspring of hypertensive parents. We hypothesized that a familial influence on the BP of the offspring exists from birth on, but becomes significant only later in childhood. We studied the influence of familial occurrence of hypertension on the BP of 3596 children aged 6 to 18 years during a 6-year follow-up. In addition, we examined the possible associations of BP variations with polymorphisms of two candidate genes for hypertension, ie, those coding for the angiotensin converting enzyme (ACE) and those coding for angiotensinogen. A positive family history of hypertension was reflected as the occurrence of higher systolic BP values from the age of 9 years and upward among the females and from the age of 12 years and upward among the males. The mean differences in BP varied from 3.2 to 5.8 mm Hg (systolic) and 2.1 to 5.9 mm Hg (diastolic) between the female offspring of normotensive and hypertensive parents and grandparents. The systolic BP values were significantly higher among females with a hypertensive history in two generations in comparison with females from normotensive families. Among the male offspring of hypertensive and normotensive families, the BP differences were inconsistent. The deletion/deletion males had higher systolic BP values than those with other ACE genotypes. In contrast, variation at the angiotensinogen gene locus was not significantly associated with BP. We conclude that parental history of hypertension is a risk factor for high blood pressure among the offspring from the ages of 9 to 12 years and upward, and hypertension within two generations may enhance this effect. Although the common genetic variation of ACE may influence blood pressure in male children and adolescents, our data do not suggest a role for the common variation of the angiotensinogen gene as a BP regulator during childhood.

Clinical guidelines and hospital discharges of children with acute urinary tract infections.

In order to evaluate the effect of the introduction of recent similar guidelines on the treatment of acute urinary tract infection (UTI) in children, and possible changes in its epidemiology, we analyzed the records of hospital discharge for acute UTI under the age of 15 years in England and Wales between 1979 and 1993 and in Finland between 1978 and 1994. Cases were defined by the ICD9 diagnostic codes 590.1 (acute pyelonephritis) and 599.0 (UTI, site not specified) for males and females according to three age groups (0-4, 5-9, and 10-14 years). We also compared the registry data on kidney transplants due to end-stage renal disease caused by recurrent pyelonephritis in the United Kingdom and Finland. In England the rate of attack of symptomatic UTI per 1,000 girls under 15 years increased from 0.74 (95% confidence interval 0.71-0.76) in 1987 to 1.32 (1.29-1.35) in 1993 (P < 0.001, test for trend). The respective figures for Finnish girls were 1.74 (1.62-1.86) in 1987 and 1.62 (1.51-1.74) in 1993 (P = 0.72). In English boys, the increase in the attack rate was from 0.38 (0.36-0.40) in 1987 to 0.70 (0.68-0.73) in 1993 (P < 0.001). In Finnish boys the respective figures were 0.74 (0.66-0.82) in 1987 and 0.88 (0.80-0.97) in 1993 (P < 0.02). The observed increases in the attack rates of UTI most probably relate to increased referral of acute UTI patients to hospitals for the recommended imaging studies rather than changing occurrence. Publication of guidelines for treatment of UTI in children, consolidating more-general awareness, may have contributed to this. The mean annual numbers of kidney transplants in the United Kingdom and Finland during 1989-1995 due to end-stage renal disease caused by pyelonephritis were of similar magnitude, i.e., 1.9 (1.6-2.3) transplants per million inhabitants in the United Kingdom and 2.8 (1.5-4.7) transplants per million inhabitants in Finland. The decreasing trend in these figures in both countries, although statistically significant only in the United Kingdom (P < 0.05, test for trend), suggests improved longterm outcome of these patients induced by better diagnosis and treatment of pyelonephritis and the diseases related to it, such as congenital malformations. According to our data, valid clinical guidelines are effective in changing clinical practice.

Varicella and varicella immunity in patients with lysinuric protein intolerance.

Two patients with lysinuric protein intolerance (LPI) had near-fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3-folds to 10-fold, increased to > 10,000 U/L and > 10,000 micrograms/L, respectively. The patients were treated with fresh frozen plasma, red-cell transfusions and intravenous acyclovir for 14 days, and recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish patients with LPI had had varicella infection that had been more severe than that in the other children in the family or in subjects in the neighbourhood and had led to hospital admission. Varicella antibodies were measured in 24 patients; 5 had no antibodies and 5 had very low antibody titres. Primary vaccination of three patients with living varicella vaccine increased antibody titres measurably in one patient. We suggest that patients with LPI who have no varicella zoster antibodies should be treated with acyclovir if exposed to varicella and should be (re)vaccinated against chickenpox.

Functional characterisation of Eskimo dog hemoglobin: I. Interaction of Cl- and 2,3-DPG and its importance to oxygen unloading at low temperature.

The oxygen binding properties of hemoglobin and some hematological parameters in Eskimo dogs (belonging to Canis lupus familiaris) in Ilulissat/Jacobshavn, Greenland were analysed. The average [2,3-DPG] and [Hb] (n = 16) were 3.14 +/- 0.34 mmol l-1 blood and 9.53 +/- 0.65 g dl-1 (1.49 mmol l-1), respectively, giving a stoichiometric ratio of 2.11 mol 2,3-DPG/mol Hb. Oxygen binding analysis carried out on hemolysate in HEPES buffer at 20 and 37 degrees C revealed a high oxygen affinity (1.2 mmHg at pH 7.4, 20 degrees C) in the desalted condition, which decreased markedly in the presence of chloride and 2,3-DPG. A low apparent equilibrium constant for the binding of 2,3-DPG (1.0 x 10(-5) mol l-1) was found at pH 7.2 and 20 degrees C in the absence of chloride. Moreover, we show that chloride ions have an additive effect on oxygen affinity in the concentration range 10-300 mmol l-1 in the presence of 3 mmol l-1 2,3-DPG at low pH and temperature (pH < 7.4 and 20 degrees C). This feature may be of physiological importance to oxygen unloading under acidotic conditions when tissue temperature is low. Thermodynamic analysis reveal that in the presence of 3 mmol l-1 2,3-DPG and 100 mmol l-1 chloride, the Eskimo dog hemoglobin exhibits a low heat of oxygenation, which places this animal close to arctic ruminants with respect to the influence of temperature on oxygen binding in vivo.

Lack of association between copper, zinc, selenium and blood pressure among healthy children.

Contradictory results have been published about the relation between copper, zinc and selenium and blood pressure (BP). To evaluate the role of these trace elements in BP regulation, we analysed the correlations between BP and copper, zinc and selenium, measured from serum, diet and hair among 3596 healthy children in a 6-year follow up. Fasting blood samples were used in serum copper, zinc and selenium analyses. The dietary intake of trace elements and energy were determined by the 48-h recall method. The hair copper and zinc analyses were performed from the naturally coloured hair samples. Correlation analysis was used to show the relation between BP and copper, zinc or selenium in each study year and during a 3- or 6-year follow-up period. The zinc-to-copper ratio in serum, diet and hair was calculated. In the correlation analyses the data was adjusted for weight and the daily intake of energy. Neither serum and diet copper or zinc, nor the zinc-to-copper ratio correlated uniformly with BP measured in the same year (correlation coefficients varying from -0.12 to 0.18) or in the subsequent years. Hair copper and zinc correlated weakly negatively with BP (correlation coefficients varying from -0.17 to -0.01). Serum selenium correlated weakly positively with systolic and diastolic BP measured in the same year (correlation coefficients varying from 0.03 to 0.14), but not with subsequent BP measured in the second or third survey. Dietary selenium had an inconsistent effect on BP (correlation coefficients varying from -0.14 to 0.26). In conclusion, copper, zinc, their ratio or selenium did not associate with BP, nor did they have any effect on subsequent BP.

Change in blood pressure during pubertal insulin resistance.

To examine the levels and relationship of blood pressure and insulin during puberty, blood pressure and serum insulin were measured in 3596 subjects, aged 3-18 y, whose pubertal status was graded according to the Tanner classification. The same study protocol was repeated in two follow-up surveys 3 and 6 y later for 2991 6-21-y-old subjects and 2799 9-24-y-old subjects, respectively. There was a 37-66% increase in insulin at Tanner stage 3 (pubic hair) among the female subjects and at Tanner stage 5 (pubic hair) among the male subjects, after which insulin started to decrease. The mean systolic and diastolic blood pressure increased steadily throughout puberty. The rise in blood pressure continued during early adulthood, despite the decrease in serum insulin. The correlation between systolic blood pressure and insulin measured in the same year was weak at each pubertal stage after standardization for weight, except among the female subjects at mid puberty. There was no relation between diastolic blood pressure and insulin. Adult systolic blood pressure could be predicted by pubertal insulin among the male subjects after adjustment for age and weight (partial correlation coefficient 0.21), but among the female subjects this relation was trivial (partial correlation coefficient 0.08). We conclude that the correlation between insulin and actual blood pressure vanishes during puberty, whereas pubertal insulin and future adult male systolic blood pressure seem to correlate.

Comparison of cyclosporin A pharmacokinetics of a new microemulsion formulation and standard oral preparation in patients with psoriasis.

Cyclosporin A (CyA) is a potent immunosuppressive drug which has shown efficacy in various skin disorders. The bioavailability of the oral CyA formulation (Sandimmun) is approximately 30%, showing high interpatient and intrapatient variability. The steady-state pharmacokinetics, efficacy and tolerability of CyA in two formulations: commercial Sandimmun soft gelatin capsules (CyA-SGC) and a newer oral formulation (Sandimmun Neoral: CyA-NOF), were compared in an open prospective study with a crossover between the two treatments in 19 patients with psoriasis. Each patient received a twice-daily treatment of CyA with a clinically effective dose of 2-5 mg/kg per day. The individual dosages were kept unchanged for at least 2 weeks before study entry and over the 42-day course of the study. At entry, patients were switched to CyA-NOF for 4 weeks and then back to CyA-SGC for another 2 weeks. Pharmacokinetic profiles were assessed at steady-state on day 14 while the patients were on CyA-NOF, and on day 42 while on CyA-SGC. Switching from CyA-SGC to CyA-NOF using 1:1 dose conversion resulted in an increased absorption of the drug. On average there was a 61% increase in maximum drug concentration (Cmax) and a 32% increase in the area under the steady-state blood concentration-time curve (AUC): Cmin was comparable in the two formulations. The increases in Cmax and AUC were associated with some increase in the clinical efficacy of the treatment. The number of adverse events reported by the patients and observed by the investigators were increased during CyA-NOF; the mean serum creatinine levels were not affected. An increased and a more consistent and predictable absorption of CyA is achieved with the new oral microemulsion formulation.