Third Year Of Treatment Research Articles

Does mycophenolate mofetil prevent extra-renal flares in systemic lupus erythematosus? Results from an observational study of patients in a single practice treated for up to 5 years

In this study, the clinical course and change in extra-renal manifestations of patients with SLE taking mycophenolate mofetil (MMF) were evaluated. The charts of 75 consecutively identified patients on MMF from a single practice were reviewed for demographics, dates of SLE diagnosis, initiation, indication or discontinuation of MMF and other medications. British Isles Lupus Assessment Group (BILAG) organ system data were identified for 3 months prior to MMF and then for the subsequent 5 years. BILAG scores for each organ system and an overall score were calculated for intervals of 6 months. The mean age of 75 subjects was 35.8 years with SLE mean disease duration of 99.2 months. Indications for starting MMF were renal (70.7%), musculoskeletal (10.6%), mucocutaneous (9.3%), cardiorespiratory (5.3%), haematologic (4%), vasculitic (2.7%), neurologic (1.3%) and other (18.7%). The mean duration of treatment was 3.3 years; 22 discontinuations occurred. Overall, there was a >50% improvement in composite BILAG scores for 49.3% (37/75) of patients in the first year of treatment and in 20% (15/75) of patients who were still on MMF at >or=5 years. Most flares occurred at second and third year of treatment. The general and renal systems have the most improvement and clinical remissions; the musculoskeletal, mucocutaneous and haematological systems have the most recurrences. Approximately, 50% and 20% of patients taking MMF showed improvement in overall lupus disease activity at both 1 and 5 years, respectively. When evaluating organ system subsets separately, MMF improved disease activity in the first year, but had little effect in preventing new organ-specific flares, with most flares taking place in second and third year of treatment.

Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis

Disease-modifying agents (DMAs), including interferon beta (IFNbeta) and glatiramer acetate (GA), are the mainstays of long-term treatment of multiple sclerosis (MS). Other potent anti-inflammatory agents like natalizumab and different types of chemotherapeutics are increasingly being used for treatment of MS, particularly in patients with breakthrough disease activity. Brain volume (BV) loss occurs early in the disease process, accelerates over time, and may be only partially affected by DMA therapy. Low-dose, low frequency IFNbeta administered once weekly and GA appear to partially reduce BV decline over the second and third years of treatment. High dose, high frequency IFNbeta demonstrated no clear effect on BV loss during this time period. Current evidence suggests that changes in BV after immunoablation may not be due entirely to the resolution of edema but may be related to potential chemotoxicity of high dose cyclophosphamide. Natalizumab reduces the development of BV decline in the second and third years of treatment. IV immunoglobulin showed a positive effect on decelerating BV reduction in relapsing and advanced stages of MS. These differences between DMAs may be explained by the extent of their therapeutic effects on inflammation and on the balance between inhibition or promotion of remyelination and neuronal repair in the CNS. We described the mechanisms of action by which DMAs induce accelerated, non-tissue-related BV loss (pseudoatrophy) in the short term but, in the long run, may still potentially lead to permanent BV decline. The effects of corticosteroid therapy on changes in BV in patients with MS help clarify the mechanisms through which potent anti-inflammatory treatments may prevent, stabilize, or induce BV loss.

Sustained Clinical Response and High Infliximab Survival in Psoriatic Arthritis Patients: A 3-year Long-Term Study

To investigate the efficacy, toxicity, and survival of infliximab in patients with psoriatic arthritis (PsA). Thirty-two patients with PsA, refractory to at least 2 disease-modifying antirheumatic drugs, were included in this prospective, open-label, uncontrolled study. All had active disease, defined as having a tender or swollen joint count > or =6, Psoriasis Area and Severity Index (PASI) scores > or =10, and erythrocyte sedimentation rate > or =28 mm Hg/h, or C-reactive protein > or =10 mg/L. The primary endpoints were the percentage of patients who achieved the Psoriatic Arthritis Response criteria (PsARC) and the improvement of PASI. Patients were treated with infliximab (5 mg/kg) at weeks 0, 2, 6, and every 8 weeks thereafter for a period of 3 years. Data concerning infliximab efficacy, tolerability, concomitant therapy, adverse events, and drug discontinuation were recorded. The clinical response according to the American College of Rheumatology (ACR) criteria as well as the disease activity for 28 joint indices score (DAS-28) were also recorded. After the third year of treatment, PsARC was achieved by 23/32 of patients, PASI 70 by 24/32, and PASI 90 by 23/32. A significant improvement of ACR and DAS-28 was noted. Clinical improvement was associated with a reduction of acute phase reactants. Eight patients withdrew from the study primarily for acute allergic reactions. After the first year, infliximab survival was 84%, while after the second year, it was 75%, which was maintained throughout the third year of treatment. Infliximab was effective, safe, and well tolerated in patients with PsA. The clinical response was maintained for a period of 3 years with high infliximab survival.

Persistent clinical response of infliximab treatment, over a 4-year period in ankylosing spondylitis

Our aim was to investigate the efficacy, toxicity, and drug discontinuation in patients with ankylosing spondylitis (AS) treated with infliximab. Thirty-five patients with AS, who were enrolled between June 2001 and December 2002 were treated with infliximab. All patients fulfilled the New York revised criteria for AS and had axial disease. Infliximab (5 mg/kg weight), was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter. If this failed to give an acceptable treatment response, the interval was shortened to 6 or 4 weeks. The patients were followed-up at predefined times according to a standardized protocol. Data concerning infliximab efficacy, tolerability, adverse events, interval, and drug discontinuation were all recorded. Clinical improvement according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% and the Ankylosing Spondylitis Assessment Study group (ASAS) 40%, and ASAS 5/6 response criteria were recorded. Infliximab treatment resulted in a rapid improvement in the BASDAI and ASAS scores in the first year of the treatment, which sustained throughout the fourth year. More specifically, after the third year of treatment 17/35 (48.6%) of patients achieved BASDAI 50% response criteria, 19/35 (54.3%) attained the ASAS 40% and 15/35 (42.9%) reached the ASAS 5/6. After the fourth year of treatment BASDAI 50% was reached by 17/35 (48.6%) of patients, ASAS 40% by 17/35 (48.6%), while ASAS 5/6 was attained by 15/35 (42.9%). The clinical improvement was associated with the reduction of acute phase reactants as measured by C-reactive protein levels. After the first year of treatment, the "survival rate" of infliximab was 94.3%, after the second year was 91.4%, after the third year was 85.7% and even after 4 years of treatment still maintained high 77.9%. Six (17.1%) patients were withdrawn during the observational period. Three because of lack of efficacy, two because of allergic reactions and one lost from follow-up. Infliximab was effective, safe, and well tolerated in patients with AS. The clinical response was maintained for a period of 4 years and over, with infliximab survival of 77.9%.

Psychoanalysis with avoidant personality disorder: A systematic case study.

This case study of process and outcome is based upon data obtained during a 5-year psychoanalysis of an adult male with avoidant personality disorder (AVPD). To date, no known systematic case studies, effectiveness studies, or randomized control trials exist for psychoanalysis in the treatment of AVPD. In this study, self-reported symptoms and observer-rated personality disorder (PD), global functioning, object relations, and psychological health were gathered at intake, after each year of treatment, and at 1-year follow-up. Process data was gathered to determine the extent to which the treatment adhered to prototypes of psychodynamic, cognitive-behavioral, and interpersonal therapy. Results indicated that the patient achieved clinically significant reductions in PD, symptom severity, and relational pathology. Gains were maintained at 1-year follow-up. The treatment significantly adhered to psychodynamic principles throughout, with some use of cognitive-behavioral and interpersonal principles in the third year of treatment. These findings warrant further investigation of psychoanalysis for AVPD and demonstrate the usefulness of assessing multiple domains of patient functioning and treatment process. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

Response to Long-Term Growth Hormone Therapy in Short Children with Reduced GH Bioactivity

Background/Aims: The aim of the present study was to investigate whether short children with normal growth hormone (GH) immunoreactivity, but reduced bioactivity (bioinactive GH) could benefit from rhGH treatment as GH deficient (GHD) patients. Methods: We evaluated 12 pre-pubertal children (8 M, 4 F), with GH deficiency-like phenotype showing normal serum GH peak levels (>10 ng/ml), measured by immunofluorimetric assay (IFMA-GH), in contrast with a reduced GH bioactivity (bio-GH), evaluated using the Nb₂ cells. We also evaluated 15 age-matched GHD pre-pubertal children (11 M, 4 F) with serum GH peak <5 ng/ml. Both groups were treated with rhGH therapy at the dose of 0.23 mg/kg/week s.c. Results: Serum bio-GH/IFMA-GH ratio at peak time for each patient during the provocative test was significantly lower in bioinactive GH than in GHD children (0.29 vs. 2.05, p = 0.00001). Recombinant human GH therapy induced a significant (p < 0.001) increase in growth rate in both groups during the first 2 years. In the third year of treatment, while growth rate in GHD children is maintained, in bioinactive GH patients it decreases remaining, however higher compared to the pre-treatment one. Conclusions:Short rhGH therapy given to selected bioinactive GH children improve growth rate and might result in greater final adult height.

Prolonged Lamivudine Treatment in Patients with Chronic Active Anti-HBe–Positive Hepatitis

The efficacy of lamivudine (LAM) at 100 mg/d for 1 year in normalizing serum ALT levels and suppressing HBV DNA has been demonstrated in many studies. However, frequent relapses make long-term results modest. In the present study, we evaluated the efficacy of LAM administered for 3 years in patients with chronic active anti-HBe-positive hepatitis. Thirty-four patients with chronic active anti-HBe-positive hepatitis were treated with LAM (100 mg) once daily for 3 years. Before treatment, all patients demonstrated serum ALT levels >2 times normal levels for >6 months and HBV DNA positivity >5 pg/mL as determined by the sandwich hybridization test for nucleic acid. Both ALT and HBV DNA were monitored during therapy. After 12 months of therapy, 24 of 34 patients (70.6%) showed evidence of HBV DNA clearance and normal ALT levels; 22 of 34 (64.7%) and 19 of 34 (55.8%) patients maintained a complete response after 2 and 3 years of therapy, respectively. The long-term LAM therapy (>1 year) was not associated with an increase in the response of intially nonresponder patients. The YMDD variant emerged in 17.6% of patients in the first year, in 35.2% during the second year, and 52.9% during the third year of treatment. LAM was well tolerated during the 3-year therapy in all patients. Patients with chronic active anti-HBe-positive hepatitis demonstrated that the LAM response rate tends to decrease over time due to the emergence of YMDD variants.

Effectiveness and tolerability of 3‐year lanreotide Autogel® treatment in patients with acromegaly

During short-term treatment, monthly subcutaneous injections of lanreotide Autogel are effective in controlling GH/IGF-1 hypersecretion and are well tolerated in patients with acromegaly. This study reports the effectiveness and the tolerability of lanreotide Autogel for at least 3 years in acromegalic patients. Fourteen patients (nine females, five males) were treated with titrated doses of lanreotide Autogel. This clinical study was an extension of a previous trial. After three fixed-dose lanreotide Autogel injections, treatment was adjusted according to mean GH and IGF-I levels. After 3 years of treatment, patients were receiving 120 (n=7), 90 (n=2) and 60 mg (n=4) monthly injections of lanreotide Autogel. Acromegalic symptoms, GH and IGF-1 concentrations were analysed at the end of lanreotide microparticle treatment, and after 4, 8, 12, 24, 30 and 36 months of lanreotide Autogel therapy. Tolerance and side-effects were monitored throughout the 3-year study. RESULTS Hormonal control (GH <or= 2.5 microg/l and age- and sex-normalized IGF-1) was achieved in six (46%) patients. With the exception of an unrelated death due to pulmonary embolism, no patient withdrew from study. The number of patients reporting digestive adverse events was seven (12 episodes) for the fixed-dose period, and four (eight episodes), two (six episodes) and one (three episodes) at the end of the first, second and third year of treatment, respectively. Persistent induration at the injection sites was reported by two patients, and histological findings were consistent with benign injection-site granulomas. New cholelithiasis or sludge occurred in five (35%) patients during the lanreotide Autogel treatment. This 3-year study shows that lanreotide Autogel is effective in controlling GH/IGF-1 hypersecretion and is well tolerated during long-term treatment of patients with acromegaly.

Three‐year follow‐up of clinical and inflammation parameters in children monosensitized to mites undergoing sub‐lingual immunotherapy

Parallel follow-up of clinical and inflammatory markers during sub-lingual immunotherapy (SLIT) is highly beneficial. Twenty-four children (age 4-16) monosensitized to house dust mite were randomized to receive either active or placebo SLIT for 1 yr in a double-blind placebo controlled design (Marcucci et al., Allergy 2003: 58: 657-62). Thereafter, for 2 yr they all received active treatment. Symptom scores for rhinitis, asthma, and drug usage were daily recorded. Eosinophil cationic protein (ECP) and tryptase in sputum and nasal secretions, serum and nasal mite-specific immunoglobulin E (IgE) were recorded before treatment and at 10-12 months intervals. Nasal ECP and nasal tryptase after specific nasal provocation tests were significantly reduced as compared to baseline values (p = 0.0043 and 0.0195, respectively) in the third year of active treatment. None of the other inflammatory parameters was increased. In placebo treated patients all these parameters tended to decrease only after switching to active treatment. Clinical scores did not improve in treated vs. placebo patients in the double-blind placebo-controlled phase of the study. In both cohorts a clinical benefit was observed as intra-group score reduction as compared to baseline. A significant difference was reached in patients treated for 2 yr for rhinitis and asthma (p = 0.0009 and 0.0019, respectively) but not for drug usage and in patients treated for 3 yr for rhinitis, asthma, and drug usage (p = 0.0105, 0.0048, and 0.02, respectively). SLIT in children monosensitized to mites reverted the spontaneous increase in nasal IgE and in local parameters of allergic inflammation. These outcomes were followed by a consolidated clinical improvement in the second and third year of treatment.

Infliximab therapy in established rheumatoid arthritis: An observational study

Purpose To investigate the efficacy, toxicity and drug discontinuation rate in an observational study of patients with established rheumatoid arthritis treated with infliximab. Subjects and methods Between September 1999 and June 2003, we enrolled 84 patients with rheumatoid arthritis who were being treated with infliximab. All patients met the American College of Rheumatology criteria for rheumatoid arthritis and had been refractory to (or did not tolerate) at least two disease-modifying antirheumatic drugs. Patients entering the study had a negative purified protein derivative skin test, were fully informed about the treatment regimen, and were followed up at predefined times according to a standardized protocol. Data concerning infliximab dosage, tolerability, adverse events, concomitant therapy, dosage interval, and drug discontinuation were all recorded. In addition, the clinical and laboratory variables according to the American College of Rheumatology 20% and 50% response criteria and the disease activity score for the 28 joint indices were also recorded. Results There were 61 women and 23 men with a mean age of 59 ± 8 years and mean disease duration of 11 ± 6 years. Seventy—five percent (63/84) were seropositive for IgM rheumatoid factor. After the first year of treatment, 84.5% of patients continued to be treated with infliximab, whereas this percentage was 73% after the second year and 59% after the third year of treatment. The American College of Rheumatology 20% response criteria was met by 59/84 (70%) of patients, and 38/84 (45%) of the patients achieved the 50% response criteria in the first year of treatment. At the second year of therapy, the American College of Rheumatology 20% response criteria were reached by 35/84 (42%) of the patients and the 50% response criteria by 27/84 (32%). At the third year of treatment with infliximab, the American College of Rheumatology 20% and 50% response criteria were achieved by 13/84 (15.5%) and 10/84 (12%) of the patients, respectively. Twenty-eight of eighty-four (33%) patients discontinued infliximab therapy. The risk of drug discontinuation decreased with the concomitant use of methotrexate. The main reasons for drug discontinuation were adverse drug reactions (16/84, 19%), followed by lack of efficacy (9/84, 11%). The main reasons for drug discontinuation due to side effects were immediate hypersensitivity reactions (9/84, 11%) and infections (6/84, 7%). Conclusion Infliximab was found to be an alternative treatment with a relatively acceptable toxicity profile, despite the fact that two patients developed pulmonary tuberculosis. After the third year of therapy, 59% of patients continued to be treated with infliximab. The concomitant use of methotrexate was associated with the continuation of infliximab therapy.

13 Survival of Hemodialysis Patients Older Than 65 years: Influence of Albumin, Hemoglobin, and Cholesterol Concentration

More and more patients over 65 years of age are starting dialysis treatment. It is understood that they are a special and more sensitive group, due to their age and correlated diseases. The aim of this work is to analyze the influence of albumin, hemoglobin, and cholesterol concentration at the beginning of treatment on survival of patients over 65 years. Between January 1, 1995 and December 31, 1999, we followed 61 patients starting hemodialysis (31 male and 30 female). All patients were over 65 years old. Their survival was monitored until June 30, 2002. They were divided into four groups, according to years of survival. In the first group were the patients who died during the first year of treatment. The second group consisted of patients who died in the second year of treatment. In the third group were patients still alive in the third year of treatment and up to the fifth year. The fourth group consist of the patients who survived longer than five years. The average albumin values (g/L) for the first group at the beginning of dialysis were 31.9 ± 5.9; for the second 35.3 ± 6.4; the third 38.1 ± 6.6 and the fourth 41.8 ± 6.7 (P = 0.017). Initial hemoglobin (g/L) was, for the first group 81.1 ± 14.3; the second group 85.7 ± 20.5; the third 86.4 ± 14.5 and the fourth 97.2 ± 6.2 (P = 0.021). Cholesterol (mmol/L) in the first group, when they started the treatment, was 4.7 ± 1.1, the second 5.1 ± 1.8, the third 5.2 ± 1.5, and the fourth 5.1 ± 0.7 (P = 0.072).From these results it is obvious that shorter survival of older patients on hemodialysis is in correlation with lower albumin and hemoglobin values in the beginning of treatment. Also, patients with shorter survival rates had lower cholesterol values, but here are no statistically significant differences. It can be concluded that there is a better prognosis for patients starting dialysis when they have good albumin, hemoglobin and cholesterol values.

P181 - Pseudo-pubertés précoces révélatrices d’un corticosurrénalome malin

Trente huit enfants ont été traités pendant au moins 2 ans pour une puberté précoce par un analogue retard du LH-RH. Ce traitement a été bien toléré. Il entraîne une régression des caractères secondaires, une diminution de la vitesse de croissance, un ralentissement de la maturation osseuse, une inhibition de la sécrétion des gonadotrophines hypophysaires et une normalisation des stéroïdes sexuels. La normalisation du rapport âge statural/âge osseux fait espérer une amélioration de la taille définitive.Chronic administration of luteinizing hormone-releasing hormone (LH-RH) is currently considered as the most appropriate therapy of precocious puberty. A delayed release preparation of D-Trp-6-LH-RH (Décapeptyl ® in microcapsules) designed to release the agonist for 28 days after intramuscular injection of 60 μg/kg body wt was given to 12 boys and 26 girls with precocious puberty. Plasma levels of gonadotropins and sex steroids were suppressed to prepubertal levels within 3 weeks, whilst pituitary responses to LH-RH test were almost abolished within 7 weeks.A significant improvement of secondary sex characteristics, as well as gonadal size, was observed within 6 months. Growth velocity (cm/yr, mean ± SD) was reduced in boys and girls from 9.9 ± 3.4 and 9.6 ± 3.3 respectively before treatment to 5.2 ± 1.0 and 5.3 ± 1.3 respectively during the third year of treatment. The mean ratio height age/bone age was just before treatment 0.91 in boys and 0.88 in girls and increased to 1 after 3 yr of treatment. This study shows that Decapeptyl in microcapsules induced a prolonged suppression of gonadal function and a relative blockade of bone maturation. A significant improvement of adult height relative to the effect of conventional treatments should be expected.

Maintenance venom immunotherapy.

Venom immunotherapy has proven to be a very effective method for the prevention of future re-sting reactions. However, initiation of the venom injection program is just the beginning. This review looks at recent papers which shed light on other issues that arise during maintenance venom immunotherapy. Prophylactic antihistamines taken before venom injections reduce the frequency of reactions and one report suggests that they may improve efficacy. The schedule of venom injections usually does not have to be adjusted for patients who develop local reactions; a very large reaction may be the exception. Patients who react to stings should have their maintenance doses increased. Most patients are able to extend the interval between injections to 8 weeks in the third year of treatment. Two groups have proposed a maintenance interval of 12 weeks for routine use. Our understanding of insect sting sensitivity continues to improve, leading to better outcomes for allergic patients.

Effects of Temperature, and Nitrogen and Sulfur Deposition, on Methane Emission from a Boreal Mire

To evaluate the effects of increased air temperature in combination with increased deposition of N and/or S on methane emission, we have raised in situ the temperature and rates of deposition of N and S in a poor fen lawn area of a boreal mixed mire. The experiment was laid out in a factorial design, where the mean daily air temperature 0.3 m above the vegetation surface was increased (by 3.6°C) using greenhouse enclosures. A significant increase in the cover of sedges was observed in the N-supplemented plots after the third year of treatment. All three experimental factors had significant effects on the methane emission. The effects of temperature and N deposition strongly interacted with the sedge cover, which was the single variable explaining most variation in methane emission. Raised temperature affected the emission positively when the sedge cover was high but showed no effect when the sedge cover was low. Nitrogen addition affected methane emission negatively when the sedge cover was high and had a zero or slightly positive effect at low sedge cover. These positive temperature and negative N interaction effects with sedge cover were likely due to changed biomass allocation patterns in the plants. The S additions had negative effects on methane emissions at ambient temperature but no effect at raised temperature. This interaction effect was possibly a result of different retention of S, since the total S concentration was higher in the S addition treatments at normal but not at raised temperature. The results stress the fact that a given variable may affect biogeochemical processes in different directions or to differing degrees depending on other variables, both experimental and natural. Most importantly, the effects of added nitrogen, but also of increased temperature, were critically dependent on the density of sedges.

EFFECTS OF TEMPERATURE, AND NITROGEN AND SULFUR DEPOSITION, ON METHANE EMISSION FROM A BOREAL MIRE

To evaluate the effects of increased air temperature in combination with increased deposition of N and/or S on methane emission, we have raised in situ the temperature and rates of deposition of N and S in a poor fen lawn area of a boreal mixed mire. The experiment was laid out in a factorial design, where the mean daily air temperature 0.3 m above the vegetation surface was increased (by 3.6°C) using greenhouse enclosures. A significant increase in the cover of sedges was observed in the N-supplemented plots after the third year of treatment. All three experimental factors had significant effects on the methane emission. The effects of temperature and N deposition strongly interacted with the sedge cover, which was the single variable explaining most variation in methane emission. Raised temperature affected the emission positively when the sedge cover was high but showed no effect when the sedge cover was low. Nitrogen addition affected methane emission negatively when the sedge cover was high and had a zero or slightly positive effect at low sedge cover. These positive temperature and negative N interaction effects with sedge cover were likely due to changed biomass allocation patterns in the plants. The S additions had negative effects on methane emissions at ambient temperature but no effect at raised temperature. This interaction effect was possibly a result of different retention of S, since the total S concentration was higher in the S addition treatments at normal but not at raised temperature. The results stress the fact that a given variable may affect biogeochemical processes in different directions or to differing degrees depending on other variables, both experimental and natural. Most importantly, the effects of added nitrogen, but also of increased temperature, were critically dependent on the density of sedges.

Ecosystems with increased carbon dioxide

No one doubts that carbon dioxide (CO2) levels in the atmosphere increased in the past century. But a great source of controversy is what happens to ecological systems when CO2 levels increase. A popular hypothesis, the greenhouse effect, posits that increased CO2 will act as a blanket, increase atmospheric temperatures and damage current ecosystem dynamics (www.greenhousenet.org). Another hypothesis, the greening theory, predicts that more atmospheric CO2 will lead to increased plant growth and increased ecosystem productivity (www.greeningearthsociety.org). Two new reports add important insight to the controversial question: what happens when atmospheric CO2 levels increase?The first study focuses on carbon sequestration when atmospheric carbon increases. Pascal A. Niklaus and colleagues1xCarbon allocation in calcareous grassland under elevated CO2: a combined 13C pulse-labelling/soil physical fractionation study. Niklaus, P.A. et al. Ecology. 2001; 15: 43–50See all References1 examined the effects of nearly doubling atmospheric CO2 levels in biotic and abiotic components of a grassland ecosystem. The group cut out sections of grassland from Switzerland in the spring, and grew them in greenhouses for the rest of the season where the researchers manipulated the atmospheric conditions. Although at elevated CO2 levels, the below-ground carbon in plants increases by nearly a third at the end of the season, the total carbon within the ecosystem does not substantially increase. Above-ground total biomass increased by 10% in the CO2 treatment, whereas the root biomass did not substantially change. The experiment illustrates that increasing carbon levels do not necessarily increase plant biomass. The group also examined soil microorganism, earthworms and soil aggregates as ecological markers. Elevated levels of CO2 results in smaller soil aggregates but does not result in any change in microbial carbon levels or earthworm composition. The experiment shows that increasing CO2 in a grassland ecosystem results in no significant increases in ecosystem carbon uptake.The second group focuses on how increases in atmospheric CO2 affect tree fecundity. Shannon LaDeau and James Clark2xRising CO2 levels and the fecundity of forest trees. LaDeau, S.L. and Clark, J.S. Science. 2001; 292: 95–98Crossref | PubMed | Scopus (107)See all References2 fumigated enriched CO2 into whole sections of loblolly pine forest (Pinus taeda) in North Carolina (USA), thereby manipulating CO2 levels in the entire ecosystem. The group examined cone and seed production as markers of tree fecundity in a forest that was nearing reproductive maturity. After four years of treatment, CO2 fumigation results in a threefold increase in mature cone production per tree, and the cones are smaller in diameter compared with nonfumigated controls. The group also collected seeds that fell around the trees. The treated trees produce three times as many seeds as non-treated controls. Also, by the third year of treatment, twice as many treated trees reached maturity compared with untreated controls.The two studies point out a surprising hypothesis. Elevation of atmospheric CO2 can lead to increased turnover of biomass but not necessarily to an increase in the level of standing biomass or carbon assimilation into the ecosystem. To test this possibility, Niklaus and colleagues could measure fecundity in their grasslands, and possibly manipulate CO2 levels in the field. LaDeau and Clark could further examine the biomass and carbon assimilation in their fumigated forests. The studies complicate the simple models of how atmospheric levels of CO2 affect plant development and ecosystems.

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

Due to their known effects on bone metabolism, vitamin D and related compounds have been proposed for the prevention of osteoporosis and fractures. To determine the effects of supplementation with Vitamin D or a Vitamin D analogue in the prevention of fractures of the axial and appendicular skeleton in elderly men or women with involutional or post-menopausal osteoporosis. We searched MEDLINE, EMBASE, CINAHL, LILACS, CABNAR, BIOSIS, HEALTHSTAR, Current Contents, The Cochrane Database of Systematic Reviews, the Cochrane Musculoskeletal Injuries Group trials register, and bibliographies of identified trials and reviews. Date of the most recent search: September 2000. Any randomised or quasi-randomised trial which compared vitamin D or a vitamin D analogue, either alone or in combination with calcium supplementation, with a placebo, no intervention, or the administration of calcium supplements, with eligible fracture outcomes, in elderly men or women with involutional or post-menopausal osteoporosis. Two reviewers independently assessed trial quality, by use of a nine item scale, and extracted data. Additional information was sought from trialists. Where possible the data were pooled. Pooling of data, where it was admissible, used pooled relative risk and fixed effects model. Almost all estimates of treatment effects are based on single studies. Administration of vitamin D3 alone without calcium co-supplementation was not associated with any reduction in incidence of hip fracture (relative risk (RR) 1.20, 95% confidence interval (CI) 0.83, 1.75) or other non-vertebral fracture. Administration of vitamin D3 with calcium co-supplementation to frail elderly people in sheltered accommodation was associated with a reduction in incidence of hip fracture (RR 0.74, 95% CI 0.60, 0.91). In healthy younger, ambulant participants the effect on hip fracture is unknown (RR 0.36, 95% CI 0.01, 8.78), although there appears to be a significant overall effect on non-vertebral fracture incidence in this group ( RR 0.46, 95% CI 0.23,0.90). Calcitriol (1,25 dihdyroxy vitamin D) was effective in reducing the incidence of vertebral deformity (RR 0.49, 95% CI 0.25, 0.95). Calcitriol was more effective than calcium in reducing the frequency of new vertebral deformities during the third year of treatment (RR 0.28, 95% CI 0.15, 0.52). 1-alpha-hydroxy vitamin D was effective in reducing the incidence of non-vertebral fractures in a single small study of elderly people whose mobility was impaired by neurological disease (RR 0.12, 95% CI 0.02, 0.95). No statistically significant effects were found for other comparisons of vitamin D or its analogues against each other, with and without calcium supplementation. Uncertainty remains about the efficacy of regimens which include vitamin D or its analogues in fracture prevention. Particularly if co-supplementation of calcium is required, significant cost differences are likely to exist between regimens. Further large randomised trials are currently being conducted to clarify the effectiveness of community fracture prevention programmes employing vitamin D supplementation.

Efficacy of amitraz applied to white-tailed deer by the '4-poster' topical treatment device in controlling free-living lone star ticks (Acari: Ixodidae).

White-tailed deer treated themselves with a commercial pour-on acaricide formulation containing 2% amitraz as they fed from an ARS-patented '4-poster' topical treatment device. Whole kernel corn attracted deer to a single device placed in each of two deer-fenced pastures. In the treatment pasture, the rollers of the treatment device were charged with the acaricide, whereas the rollers of the device in the other pasture remained untreated. Deer were allowed to use the '4-posters' during periods of tick activity beginning in early to midspring and lasting through late summer to early fall for three consecutive years. Pretreatment sampling of adults and nymphs with dry-ice traps and larval masses with flip cloths showed no significant differences in population indices between the two pastures; however, after the third year of treatment, control of nymphal and adult ticks in the treated pasture was 91.9 and 93.7%, respectively, when compared with the untreated pasture. Control of larval masses increased from 68.4% in year 1 to 96.4% in year 2, but declined to 88.0% in year 3, probably because of the presence of feral hogs. This study demonstrated that application of amitraz to white-tailed deer through free-choice interaction with a '4-poster' device significantly reduced the abundance of free-living lone star ticks in a deer-fenced experimental pasture. Moreover, the yearly pattern of incremental increases in control and the final percentage control values for all three parasitic life stages in this topical application study were similar in magnitude to that observed in a previously conducted study in which the systemic acaricide ivermectin was used to reduce populations of free-living ticks by controlling ticks on deer.

Utilisation of mental health services and costs of patients with schizophrenia in three areas of Spain.

The analysis of the costs of schizophrenia and its treatment under different mental health care structures will facilitate the improved allocation of the limited resources available for the treatment of schizophrenia. The research we present compares health service use and total health care costs of three cohorts of subjects with schizophrenia which are representative of three areas of Spain (Burlada in Navarra, Cantabria and the Eixample of Barcelona). We selected first-time contacts with any psychiatric service who received a diagnosis of schizophrenia. Subjects were evaluated in the third year after onset. The mean number of out-patient visits per patient per year was 10.7 and the mean in-patient days were 9.5. The mean direct cost per patient in the third year of treatment was US$2243. Costs were higher for single subjects and for people who had a relapse. Costs of subjects with better functioning were lower than costs of subjects with a worse state. Direct costs of care in Spain were lower than the reported figures from other western European countries. Costs were greater in the two centres with greater community mental health service development. Some of the findings may be explained by service availability.

The limited effects of antipsychotic medication on schizophrenia relapse and adjustment and the contributions of psychosocial treatment

Whether psychosocial treatment adds substantially to the prophylactic efficacy of maintenance antipsychotic monotherapy requires a more accurate estimate of relapse risks than those contained in recent reviews. A reappraisal of the literature suggests a 1-year, post- hospital, relapse rate of 40% on medication, and a substantially higher rate among patients who live in stressful environments, rather than earlier estimates of 16%. Relapse rates of 65% at 1 year and over 80% by 2 years among drug discontinued or placebo substituted outpatients are also more accurate than the 53% relapse rate previously estimated. When psychosocial treatment is added to maintenance chemotherapy, there is compelling evidence that relapse rates are reduced by as much as 50% compared with relapse associated with medication and standard care. However, psychosocial treatment without medication is as ineffective as placebo. The additive effects appear greater for recent, theoretically based psychosocial approaches than earlier atheoretical, altruistic forms of caring. However, effects vary according to the patient's clinical state, the nature and timing of the intervention, and the presence of environmental stressors. Regarding adjustment, very little definitive information regarding psychosocial treatment effects has existed until recently. A novel, disorder-relevant approach has now been shown to have broad and significant effects on social adjustment compared with medication and support. However, the magnitude of effects is not fully realized until a third year of treatment: a distinct challenge in the era of managed care. Atypical antipsychotics and more definitive psychosocial strategies that target social cognitive deficits hold promise for enhanced outcomes in the next generation of studies.