Outbreak of Cryptosporidium hominis in northern Sweden: persisting symptoms in a 5-year follow-up.

In 2010-2011, a waterborne outbreak of the parasite, Cryptosporidium hominis, affected approximately 27,000 inhabitants in the city of Östersund, Sweden. Previous research suggested that post-infectious symptoms, such as gastrointestinal symptoms and joint pain, could persist for up to 2 years after the initial infection. In this study, we investigated whether the parasite caused post-infectious sequelae for up to 5 years after the outbreak. Prospective cohort study. A randomly selected cohort of individuals residing in Östersund at the time of the outbreak was sent a postal questionnaire in 2011. Responders were sent a follow-up questionnaire in 2016 and completed items on whether they experienced a list of symptoms. We examined whether outbreak cases were more likely than non-cases to report post-infectious symptoms 5 years later. We analysed data using logistic regression and calculated odds ratios with 95% confidence intervals. The analysis included 626 individuals. Among the 262 individuals infected during the outbreak, 56.5% reported symptoms at follow-up. Compared to non-cases, outbreak cases were more likely to report watery diarrhoea, diarrhoea, swollen joints, abdominal pain, bloating, joint discomfort, acid indigestion, alternating bowel habits, joint pain, ocular pain, nausea, and fatigue at the follow-up, after adjusting for age and sex. Our findings suggested that cryptosporidiosis was mainly associated with gastrointestinal- and joint-related post-infectious symptoms for up to 5 years after the infection.

Hand-held cardiac ultrasound examinations performed in primary care patients by nonexperts to identify reduced ejection fraction.

BACKGROUND: Early identification of patients with reduced left ventricular ejection fraction (LVEF) could facilitate the care of patients with suspected heart failure (HF). We examined if (1) focused cardiac ultrasound (FCU) performed with a hand-held device (Vscan 1.2) could identify patients with LVEF < 50%, and (2) the distribution of HF types among patients with suspected HF seen at primary care clinics. METHODS: FCU performed by general practitioners (GPs)/GP registrars after a training programme comprising 20 supervised FCU examinations were compared with the corresponding results from conventional cardiac ultrasound by specialists. The agreement between groups of estimated LVEF < 50%, after visual assessment of global left ventricular function, was compared. Types of HF were determined according to the outcomes from the reference examinations and serum levels of natriuretic peptides (NT-proBNP). RESULTS: One hundred patients were examined by FCU that was performed by 1-4 independent examiners as well as by the reference method, contributing to 140 examinations (false positive rate, 19.0%; false negative rate, 52.6%; sensitivity, 47.4% [95% confidence interval [CI]: 27.3-68.3]; specificity, 81.0% [95% CI: 73.1-87.0]; Cohen's κ measure for agreement = 0.22 [95% CI: 0.03-0.40]). Among patients with false negative examinations, 1/7 had HF with LVEF < 40%, while the others had HF with LVEF 40-49% or did not meet the full criteria for HF. In patients with NT-proBNP > 125 ng/L and fulfilling the criteria for HF (68/94), HF with preserved LVEF (≥50%) predominated, followed by mid-range (40-49%) or reduced LVEF (< 40%) HF types (53.2, 11.7 and 7.4%, respectively). CONCLUSIONS: There was poor agreement between expert examiners using standard ultrasound equipment and non-experts using a handheld ultrasound device to identify patients with reduced LVEF. Asides from possible shortcomings of the training programme, the poor performance of non-experts could be explained by their limited experience in identifying left ventricular dysfunction because of the low percentage of patients with HF and reduced ejection fraction seen in the primary care setting. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02939157). Registered 19 October 2016.

The idiopathic normal-pressure hydrocephalus Radscale: a radiological scale for structured evaluation.

BACKGROUND AND PURPOSE: Despite the important role of imaging in diagnosing idiopathic normal-pressure hydrocephalus (iNPH), a structured overall assessment of radiological signs is still lacking. The purpose of this study was to construct a radiological scale, composed of morphological signs of iNPH, and compare it with clinical symptoms. METHODS: In this prospective, population-based study of iNPH, 168 individuals (93 females) [mean age 75 (range 66-92) years] underwent computed tomography of the brain and a neurological examination with assessment of clinical symptoms according to Hellström's iNPH scale. Two radiologists, blinded to clinical data, independently evaluated and measured eight radiological parameters, i.e. Evans' index, callosal angle, size of temporal horns, narrow high-convexity sulci, dilated Sylvian fissures, focally dilated sulci, peri-ventricular hypodensities and bulging of the lateral ventricular roof. RESULTS: In a linear regression model, all parameters except ventricular roof bulging were significantly associated with clinical iNPH symptoms. The seven remaining parameters were summarized into a total iNPH Radscale score ranging from 0 to 12. There was a significant correlation (r = 0.55, P < 0.001) between the total iNPH Radscale score and clinical symptoms. The inter-rater agreement for the included radiological parameters was high (intraclass correlation, 0.74-0.97). CONCLUSION: The iNPH Radscale may become a valuable diagnostic screening tool, allowing a structured radiological assessment. A high iNPH Radscale score together with clinical symptoms should raise suspicion of iNPH, motivating further evaluation for shunt surgery.

Challenges in diagnosing normal pressure hydrocephalus: Evaluation of the diagnostic guidelines.

PURPOSE: To evaluate the present diagnostic guidelines of idiopathic normal pressure hydrocephalus (iNPH) in a sample from the general population. METHODS: A total of 168 individuals (93 females, 75 males), mean age 75 years (range 66-92) with and without symptoms of iNPH underwent a CT-scan of the brain, a neurological examination with assessment of the triad symptoms, i.e. gait disturbances, memory impairment and urgency incontinence. The participants were then diagnosed as "unlikely", "possible" and "probable" iNPH according to the American-European and the Japanese guidelines, respectively. Separately, a senior consultant in neurology diagnosed each patient based on the overall clinical picture. RESULTS: Obtaining a diagnosis of "probable iNPH" was three times more likely according to the American-European guidelines (n = 35) compared to the Japanese guidelines (n = 11) or the neurologist (n = 11). The concordance was highest (Kappa = 0.69) between the Japanese guidelines and the neurologist. CONCLUSIONS: Considerable discrepancies were found when diagnosing iNPH according to two international guidelines and a neurologist, respectively. The Japanese guidelines, which include a minimum of two triad symptoms, were most concordant with the neurologist. As a step towards widely accepted, standardized diagnostic criteria, we suggest a revision of the current guidelines, preferably into one common diagnostic system.

Crystal structure of 1-butyl-2,3-di-methyl-imidazolium dicarba-7,8-nido-undeca-borate.

In the title mol-ecular salt, C9H17N2 (+)·C2H12B9 (-), the carborane cage has a bridging B-H-B bond on the open B3C2 face. The butyl side chain of the cation adopts an extended conformation [C-C-C-C = 179.6 (1)°]. In the crystal, the imidazolium ring is almost coplanar with the open face of the carborane anion. The cations stack in the [010] direction and the dihedral angle between the imidazolium rings of adjacent cations is 68.45 (6)°. The butyl chains extend into the space between carborane anions.

Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001-2004 NHANES.

AIMS: To evaluate the association between vitamin D insufficiency and peripheral neuropathy in a nationally representative sample of adults with diagnosed diabetes. METHODS: Vitamin D concentrations, medical examination variables and questionnaire results from the 2001-2004 National Health and Nutrition Examination Survey were analysed for adults ≥ 40 years old with diagnosed diabetes (unweighted n = 591, weighted n = 8.82 million). Neuropathy was defined as self report of peripheral neuropathy symptoms of painful sensation, tingling, numbness or loss of feeling in hands or feet. Additionally, Semmes-Weinstein monofilament test results were used as an indicator of neuropathy. Insufficient vitamin D was characterized as < 30 ng/ml. RESULTS: In the weighted population, 81% of adults with diabetes had vitamin D insufficiency. Vitamin D insufficiency was more common among Hispanics (92%) and non-Hispanic black people (98%) than among non-Hispanic white people (76%). Within the 3 months preceding the questionnaire, 50% reported experiencing pain or numbness (paresthesia) in their hands or feet; 37% reported pain or tingling in hands or feet; and 38% reported numbness or loss of feeling in hands or feet. Eight per cent had 4-6 insensate areas on their feet as determined by the Semmes-Weinstein monofilament test. Logistic regressions demonstrate vitamin D insufficiency is associated with the adjusted composite paresthesia measure (odds ratio 2.12; 95% CI 1.17-3.85) and the adjusted numbness measure (odds ratio 2.04; 95% CI 1.18-3.52). CONCLUSIONS: Vitamin D insufficiency is associated with self-reported peripheral neuropathy symptoms even after adjusting for demographic factors, obesity, co-morbidities, use of medications for neuropathy and diabetes duration and control.

An explorative study of low levels of allergen-specific IgE and clinical allergy symptoms during early childhood.

BACKGROUND: Early identification of children at risk for later development of allergic disease is essential for early intervention and initiation of proper treatment and management. OBJECTIVE: To investigate the relationship between low levels (0.1-0.7 kU(A) /l) of IgE sensitization to food and inhalant allergens and symptoms of eczema, rhinitis, and asthma from birth to 5 years of age. METHODS: Children (268) were followed prospectively from birth to 5 years of age with physical examinations and measurements of s-IgE at 6, 12, 24, and 60 months of age. RESULTS: Seventy-four percent of the children with low levels of s-IgE to egg and/or milk at the age of 6 months were still sensitized to one or more allergens at age 2 years. Eighty-four percent of the children with low levels of s-IgE to any of the studied allergens at 12 months of age were still sensitized at age 5. The low levels of egg and milk s-IgE also significantly increased the risk for eczema at the same age and also increased the risk for eczema at 2 years of age. CONCLUSION: Low levels of s-IgE can be detected from the age of 6 months and are related to further IgE sensitization. The low levels seem to be of importance for both the association to present symptoms and for prediction of future allergic symptoms, especially eczema during early infancy. A detectable s-IgE level, albeit low, could be a clear signal that the immune system is alerted and should be followed.

Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score.

BACKGROUND: Allergic sensitisation increases the risk for asthma development. In this prospective birth cohort (Environment and Childhood Asthma) study, we hypothesized that combining quantitative measures of IgE antibodies (Sigma-IgE) and Severity score of obstructive airways disease (OAD) at 2 years of age (Severity score) is superior to predict current asthma (CA) at 10 years than either measure alone. Secondarily, we assessed if gender modified the prediction of CA. METHODS: A follow-up study at 10 years of age was performed in 371 2-year-old children with recurrent (n = 219) or no (n = 152) bronchial obstruction with available serum analysed for Sigma-IgE to common food and inhalant allergens through a panel test, Phadiatop Infant) (Phadia, Uppsala, Sweden). Clinical variables included allergic sensitisation and exercise testing to characterise children with CA vs not CA at 10 years and the Severity score (0-12, 0 indicating no OAD) was used to assess risk modification. RESULTS: Severity score alone explained 24% (Nagelkerke R(2) = 0.24) of the variation in CA, whereas Sigma-IgE explained only 6% (R(2) = 0.06). Combining the two increased the explanatory capacity to R(2) = 0.30. Gender interacted significantly with Sigma-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Sigma-IgE for CA at 10 years was significant in boys only. CONCLUSION: Combining Sigma-IgE to inhalant allergens and Severity score at 2 years was superior to predict asthma at 10 years than either alone. Severity score predicted CA in both genders, whereas Sigma-IgE significantly predicted CA in boys only.

Genetic variants of TNFSF4 and risk for carotid artery disease and stroke.

In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730 +/- 30 vs 330 +/- 65 arbitrary units, p < 0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-alpha; 460 +/- 110 vs 133 +/- 8 arbitrary units, p < 0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.

Quantification of atopy and the probability of rhinitis in preschool children: a population-based birth cohort study.

BACKGROUND: Atopy quantification using IgE levels/skin test diameter (SPT-MWD) may better predict the expression of rhinitis than using atopy as a dichotomous variable. OBJECTIVE: To investigate the association between the presence, temporal pattern and severity of rhinitis in preschool children and specific IgE levels/SPT-MWDs. METHODS: Children were followed prospectively to age 5 years in a whole-population birth cohort study. We administered questionnaires (n = 815), skin prick tested children (n = 717) and measured specific serum IgE (n = 478) to inhalant and food allergens. Main outcomes were current rhinitis (CR) and current rhinoconjunctivitis (CRC). RESULTS: The prevalence of CR and CRC was 26.1% and 12.1%, respectively. The risk of CR and CRC increased significantly with increasing IgE to grass, mite and cat; CRC was also associated with increasing IgE to dog and peanut. Similarly, increasing SPT-MWDs to inhalant allergens were significantly associated with CR and CRC. This association was also shown for grass within the group of atopic children. Perennial and seasonal rhinitis were associated with increasing IgE/SPT-MWD to mite and grass, respectively. Moderate/severe rhinitis was associated with increasing IgE/SPT-MWD to grass. In a multivariate analysis, increasing levels of IgE/SPT-MWD to grass were the strongest independent predictors of both CR (for IgE: OR 1.42, 95% CI 1.23-1.64, P < 0.001) and CRC (for IgE: 1.51, 1.30-1.76, P < 0.001). CONCLUSION: The probability of CR/CRC increases with increasing specific IgE levels or SPT-MWD. With respect to allergic rhinitis, the absolute levels of specific IgE antibody or the size of SPT wheal offer more information than just the presence/absence of sensitization.

Sensitization to different pollens and allergic disease in 4-year-old Swedish children.

BACKGROUND: Although the relationship between sensitization to different inhalant allergens in adolescents and adults has been intensively studied, information concerning sensitization in children is scarce in particular to pollens. OBJECTIVES: In 4-year-old children to elucidate the pollen immunoglobulin (IgE) antibody profile (birch only, timothy only and combinations of three pollens (birch, timothy or mugwort) and to relate the results to other inhalant and food allergens, as well as the presence of allergic diseases. METHODS: A total of 2551 4-year-old children belonging to a prospective birth cohort, which has been followed longitudinally (BAMSE), were investigated with respect to IgE antibodies to pollen and other inhalant and food allergens, and expression of allergic disease, based on questionnaire data. RESULTS: Eleven percent (n=285) of the children were sensitized to pollen. Birch was the dominating cause of pollen sensitization (birch sensitization only, n=133); followed by timothy grass pollen (n=56) and a combination of two (n=64) or three (n=30) pollens. A remarkably high proportion of the children sensitized only to birch was also sensitized to other inhalant allergens. This was not seen for children sensitized only to timothy. The highest frequencies of IgE reactivity to food were found in the group of children sensitized to the combination of birch, timothy and mugwort pollen. Children sensitized to timothy only, exhibited symptoms of allergic disease significantly less frequently compared with children sensitized to birch only. Sensitization to birch pollen was found to be closely associated with rhinitis and eczema compared with asthma. The highest frequency of asthma and/or rhinitis and/or eczema was reported in children sensitized to at least two pollens. CONCLUSION: Our results demonstrate that birch is the dominating source of pollen sensitization at the age of four in Sweden. This might associate with the pattern of sensitization to other inhalant and food allergens as well as influence on the expression of allergic disease in this particular age group.

Passive IgE-sensitization by blood transfusion.

BACKGROUND: To study the mechanisms of passive sensitization of patients receiving plasma containing IgE antibodies to a defined allergen. METHODS: When required for medical reasons, regular donor plasma with IgE antibodies to timothy grass allergen (8-205 kU(A)/l), was given. Kinetics of IgE antibodies in the recipients' serum and his/her basophil allergen threshold sensitivity, CD-sens, was monitored up to 2-3 weeks after transfusion. The IgE antibodies were quantitated by ImmunoCAP. The CD-sens in plasma recipients, determined by CD63 up-regulation, was measured by flow cytometry and compared to CD-sens of patients with allergic asthma and/or rhinitis. RESULTS: There was a significant correlation (r = 0.98; P < 0.001) between amount of IgE antibody given and recipient serum peak concentration. The T(1/2) for IgE antibody in circulation was 1.13 days (95% confidence limit 0.35-1.91 days). The recipients became CD-sens positive already 3 h after transfusion. The CD-sens peak was observed after 3.4 days and the value were correlated (r = 0.68; P < 0.02) to the amount of IgE antibody transfused and were of the same magnitude as found in allergic patients. The T(1/2) of CD-sens indicated two populations of basophils; one with a CD-sens decrease T(1/2) of 4 days and one of 10 days. CONCLUSION: Transfused IgE antibodies will sensitize mast cells and basophils to CD-sens levels similar to those of allergic patients. The recipients expressed 'slow' or 'rapid' CD-sens decline, indicating two different basophil populations. After transfusion of plasma with >10 kU(A)/l IgE antibody the recipient could have allergen reactive basophils for up to 7 weeks.

Quantitative analysis of IgE antibodies to food and inhalant allergens in 4-year-old children reflects their likelihood of allergic disease.

BACKGROUND: It is well established that early diagnosis of allergic disease is warranted. METHODS: In a prospective birth cohort study (BAMSE) 3743 children at 4 years of age were included. Children were classified as having any allergic disease, e.g. asthma, suspected allergic rhinitis (suspAR), eczema or oro-gastro-intestinal symptoms with questionnaire. Blood was obtained from 2612 of these children and analysed for IgE antibodies (ab) towards 14 common food and airborne allergens. RESULTS: Positive IgE ab results were found in 38% of the children with any allergic disease, whereas such IgE ab results were found in 17% among those without any allergic disease. Furthermore, among children with any allergic disease the median summated IgE ab levels were 10.7 kU(A)/l compared with 1.5 kU(A)/l among those without such symptoms. The highest IgE ab levels were found to birch, peanut, cat and horse. When the sum of the IgE-ab levels towards the selected allergens was at least 34 kU(A)/l, or, alternatively, more than four allergen tests were positive, there was a 75% likelihood of identifying the individual with any allergic disease. To identify those with asthma, as well as those with suspAR, a significant interaction was found for the combination of the sum of IgE-ab levels and number of allergens positive at test. For eczema only, the number of positive allergens at test was associated to the likelihood of such disease. CONCLUSIONS: In children, 4 years of age, allergic disease was frequently not associated with the presence of single positive IgE antibody results, whereas increased IgE ab levels were significantly more prevalent among those with allergic disease. Thus, testing a certain profile of airborne and food allergens, and utilizing the sum of the IgE-ab levels in combination with the number of allergens positive at tests, may represent a more efficient diagnostic tool then to use just single positive IgE-ab results.

Antibody profiles and self-reported symptoms to pollen-related food allergens in grass pollen-allergic patients from northern Europe.

BACKGROUND: Most studies on pollen-related food allergy have so far focused on the association of birch/weed pollen allergens and plant food allergy. The aim of this study was to elucidate the allergen spectrum among a group of grass pollen-allergic patients from northern Europe and to relate the results to clinical histories of pollen-related food allergy. METHODS: Fifty-eight grass pollen-allergic patients answered a questionnaire regarding allergy to foods. Blood samples were taken to test IgE-reactivity to a large panel of pollen allergens and pollen- and nonpollen-related food allergens using crude allergen extracts and recombinant and native allergens. RESULTS: Three different groups of grass pollen-allergic patients were identified according to their IgE antibody profile: a grass pollen group only (19%), a grass and tree pollen group (29%) and a grass, tree and compositae (pan-) pollen group (48%). No sensitization to Bet v 1 as well as almost no IgE to plant food was observed in the grass pollen group. In contrast, nearly all patients in the two tree-related groups had IgE to Bet v 1, which reflected the high frequency of adverse reactions to typical birch-related food in these groups. Only four patients belonging to the pan-pollen group displayed IgE to profilin Phl p 12/Bet v 2. Patients in the pan-pollen group reported significantly more symptoms to food allergens compared with patients in the two other groups. The most frequently reported symptom was the oral allergy syndrome. CONCLUSIONS: Sensitization to grass pollen alone is rare among grass pollen-allergic patients from northern Europe. The majority of patients are in addition sensitized to birch (Bet v 1), which seems to be closely related to their pollen-derived food allergy. The study highlights the advantage of using well-defined allergen molecules for the diagnosis of cross-reactivity between pollen and food allergens.

A further evaluation of the clinical use of specific IgE antibody testing in allergic diseases.

BACKGROUND: The evaluation and interpretation of the results from blood tests measuring specific immunoglobulin E (IgE) antibody concentration is currently made using the dichotomized result from the test despite a quantitative result is obtained. It has been shown that different levels of IgE antibodies, assessed by blood test and skin prick test, may have a relation to presence of symptoms, implying that there is more information in a quantitative result than in the dichotomous--positive or negative. OBJECTIVE: To investigate the clinical utility of quantification of IgE antibodies in the diagnosis of allergic patients and whether such procedure has any advantage to the presently dichotomously used sensitivity and specificity at a fixed cut-off. METHODS: Data from a previously published study (R. Paganelli, I.J. Ansoteugi, J. Sastre, C.-E. Lange, M.H.W.M. Roovers, H. de Groot, N.B. Lindholm, P.W. Ewan, Allergy, 1998; 53) analysing diagnosis of allergic patients in four different clinics were re-evaluated. In the original study consecutive patients with suspected IgE-mediated allergy had been examined and evaluated according to the clinical routine at each clinic, using case history, physical examination, skin tests and laboratory tests, except the test to be evaluated, and given a "doctors' allergen-specific diagnosis" as positive or negative. In the present study the relation between "doctors' allergen-specific diagnosis", expressed as pos/neg, and the quantitative levels of specific IgE antibody concentration was analysed using a logistic regression model. This presentation of results was also compared with the more common characteristics of sensitivity and specificity, and also with Receiver-operator characteristics (ROC) curves. RESULTS: The used logistic model described the relationship between allergen-specific diagnosis in each study and the levels of IgE antibodies. The shape of the curve illustrated the physicians' disposition for a positive diagnose in the study, in relation to the specific IgE antibody level. Differences in the shape of the curve was found both between allergens within clinics and between clinics for the same allergen. No association could be demonstrated between prevalence and shape of the curve. CONCLUSIONS: Conventional sensitivity/specificity figures or ROC concepts only use the qualitative statement of whether IgE is present or not. A risk assessment using the quantitative level of IgE antibody to an allergen increases the utility of the information in clinical context compared with a qualitative statement of whether IgE is present or not. The quantification demonstrated the link between specific IgE antibodies and allergic reactions. The use of objective, well performing quantitative tests should help improve diagnostic accuracy and might provide a way for the patient to understand and manage his or her daily situation and risk for reactions.

The health and cost effects of substituting home care for inpatient acute care: a review of the evidence.

BACKGROUND: There is much interest in reducing hospital stays by providing some health care services in patients' homes. The authors review the evidence regarding the effects of this acute care at home (acute home care) on the health of patients and caregivers and on the social costs (public and private costs) of managing the patients' health conditions. METHODS: MEDLINE and HEALTHSTAR databases were searched for articles using the key term "home care." Bibliographies of articles read were checked for additional references. Fourteen studies met the selection criteria (publication between 1975 and early 1998, evaluation of an acute home care program for adults, and use of a control group to evaluate the program). Of the 14, only 4 also satisfied 6 internal validity criteria (patients were eligible for home care, comparable patients in home care group and hospital care group, adequate patient sample size, appropriate analytical techniques, appropriate health measures and appropriate costing methods). RESULTS: The 4 studies with internal validity evaluated home care for 5 specific health conditions (hip fracture, hip replacement, chronic obstructive pulmonary disease [COPD], hysterectomy and knee replacement); 2 of the studies also evaluated home care for various medical and surgical conditions combined. Compared with hospital care, home care had no notable effects on patients' or caregivers' health. Social costs were not reported for hip fracture. They were unaffected for hip and knee replacement, and higher for COPD and hysterectomy; in the 2 studies of various conditions combined, social costs were higher in one and lower in the other. Effects on health system costs were mixed, with overall cost savings for hip fracture and higher costs for hip and knee replacement. INTERPRETATION: The limited existing evidence indicates that, compared with hospital care, acute home care produces no notable difference in health outcomes. The effects on social and health system costs appear to vary with condition. More well-designed evaluations are needed to determine the appropriate use of acute home care.

Home-based management can achieve intensification cost-effectively in type I diabetes.

BACKGROUND: Newly diagnosed insulin-dependent diabetic children are most often admitted to hospital for education and insulin management and subsequently followed in outpatient clinics or office settings. However, most could be managed at home, given adequate family and health care team support and subsequent follow-up facilitated by home-based nursing intervention. We conducted a randomized trial of clinical, psychosocial, and cost effects of home-based management in a 2-year follow-up study of newly diagnosed diabetic children. METHODS: Sixty three patients were randomly assigned to traditional hospitalization and outpatient follow-up (hospital-based group) or home management (home-based group). Treatment differences between the two groups consisted of duration of initial hospital stay, site and timing of initial teaching, and nature and extent of subsequent nursing follow-up. Metabolic control was assessed by means of quarterly glycosylated hemoglobin measurements for 24 months and then at 36 months. Diabetes-related adverse events, knowledge of diabetes, adherence to the diabetes regimen, psychosocial impact, and social (total) costs incurred were assessed for 24 months. FINDINGS: Glycosylated hemoglobin concentrations were significantly lower in the home-based group at 12 to 24 months and at 36 months. Both groups had comparable numbers of diabetes-related adverse events. There were no significant group differences in psychosocial impact. Parents in the home-based group spent significantly fewer hours on diabetes care and incurred significantly lower out-of-pocket expenses during the 1st month. Health care sector costs were significantly higher. Hospital costs were $889 higher, and government costs $890 higher per child. Social (total) costs were only $48 higher per case (NS) with home care when parents' time was valued at $11.88 per hour. INTERPRETATION: Home-based management for newly diagnosed diabetic children can result in better metabolic control and similar psychosocial outcomes compared with traditional hospital- and clinic-based care without notable effects on social (total) costs.

An economic evaluation of home care for children with newly diagnosed diabetes: results from a randomized controlled trial.

OBJECTIVE: This study was undertaken to determine the health and cost effects of using home care to treat newly diagnosed Type I diabetic children rather than traditional inpatient hospital care. There had been no well-designed evaluations of home care for such children, and very few for children with other health conditions. METHODS: Sixty-three children seen at the Montreal Children's Hospital were randomly assigned at diagnosis to home care or traditional inpatient care. The children in the former group were discharged once their metabolic condition stabilized; insulin adjustments and teaching were done in their homes by a trained nurse. The children in the latter group remained hospitalized for insulin adjustments and teaching. All were followed for 24 months. The cost effects were estimated using hospital and parental data. RESULTS: Social costs were only $48 higher with home care. It had little effect on social costs, because the increased costs of health care services with home care ($768) were largely offset by parental cost savings ($720). Home care improved the children's metabolic outcomes without adversely affecting their psychosocial outcomes. CONCLUSIONS: Using home care to reduce hospital stays for children with newly diagnosed Type I diabetes improved the children's health outcomes without significantly increasing social costs.

Inhibition of neutrophil phagocytosis and enzyme release by hyaluronic acid.

Hyaluronic acid at a concentration found in normal joints (4 mg/ml) inhibited the uptake of aggregated IgG by human peripheral blood polymorphonuclear leukocytes, but concentrations of hyaluronic acid found in inflammatory joints (1 mg/ml) did not. Similarly, hyaluronic acid at 4 mg/ml, but not 1 mg/ml, inhibited the release of lysozyme from aggregated IgG stimulated polymorphonuclear leukocytes. beta-Glucuronidase release was inhibited by both concentrations of hyaluronic acid. Physiological concentrations of hyaluronic acid inhibit this model system for the fluid phase of rheumatoid arthritis and hyaluronic acid may be an important immunomodulating substance in the rheumatoid joint.