Alison Markwick

A Randomized Controlled Trial of the Cost‐Utility of Second‐Generation Antipsychotics in People with Psychosis and Eligible for Clozapine

OBJECTIVE To assess whether clozapine is likely to be more cost-effective than other second-generation antipsychotics (SGAs) in people with schizophrenia. METHODS An integrated clinical and economic multicenter, rater-blind, randomized controlled trial (RCT) compared clozapine to the class of other SGAs, using the perspectives of the National Health Service, social support services, and patients. The practice setting was secondary and primary care in the United Kingdom; patients were followed for 1 year. Incremental cost-effectiveness ratios (ICERs), net benefit statistics, and cost acceptability curves were estimated. RESULTS The ICER for clozapine was 33,240 pound per quality-adjusted life-year (QALY) (range 23,000-70,000 pound for the sensitivity analyses). The proportion of simulations when clozapine was more cost-effective than other SGAs reached 50% if decision-makers are prepared to pay 30,000 pound to 35,000 pound per QALY. This is at the top of the range of acceptable willingness-to-pay values per QALY implied by decisions taken by the National Institute for Health and Clinical Excellence (NICE). CONCLUSIONS This study adds to a limited body of evidence comparing clozapine to other SGAs and is the first economic and clinical RCT to compare clozapine to the class of other SGAs using the lower cost of generic clozapine and a pragmatic trial design. Policy decisions by the NICE suggest that additional reasons would be needed to accept clozapine as effective and efficient if it had a high probability of having ICERs more than 35,000 pound per QALY. The results and limitations of the analysis suggest that there is still a need for further economic evaluation of clozapine.

Attitudes to atypical and conventional antipsychotic drug treatment in clinicians participating in the cutlass study

Objectives To examine clinicians’ attitudes regarding the relative benefits and risks of conventional and atypical antipsychotic medication, and the perceived validity of the CUtLASS study. To examine the attitudes of participant clinicians’ regarding the operation and administration, and the potential clinical impact of the findings. Method Two hundred and sixty-two clinicians were each sent an anonymous questionnaire, and invited to indicate whether they agreed or disagreed with each of to nine statements (from agree to disagree). Results Of the 112 clinicians who responded, 71% supported the CUtLASS study. Thirty-nine percent agreed with the statement that the clinical efficacy of atypicals was superior to conventional antipsychotics, while 27% disagreed and 34% were undecided. Thus, two-thirds of participating clinicians revealed no uncertainty on a key question being tested in the CUtLASS study. Further, the vast majority (97%) considered that atypicals were associated with less severe side effects. Conclusions In clinical studies, recruitment strategies relying on referrals from clinicians may find that some clinicians identify fewer patients than expected. This can lead to a relatively low yield of potential study subjects and possibly a selection bias. Surveys of clinicians approached to participate in clinical studies provide a potential mechanism to explore attitudes relevant to participant recruitment.

A randomised, controlled trial of new atypical drugs versus clozapine in treatment-resistant schizophrenia

Background: A single-blind, multicentre RCT compared the class of new (non-clozapine) atypical drugs with clozapine in patients in the NHS whose medication was being changed because of poor clinical response to two or more antipsychoticdrugs.Methods: The primary outcome was the Quality of Life Scale. Secondary clinical outcomes included symptoms (PANSS), side effects and participant satisfaction. Economic outcomes were costs of health and social care and a utility measure. A total of 136 (98% of the planned sample) participants were randomised. Followup at 52 weeks, blind to treatment allocation, was complete in 87%.Results: The intent to treat comparison of new atypicals compared with clozapine in people with more narrowly defined treatment resistance showed an advantage for commencing clozapine in quality of life (QLS) at trend level ( p = 0.08) and insymptoms (PANSS), that was statistically significant ( p = 0.01), at 1 year. Clozapine showed approximately a 4-point advantage (not statistically significant) on QLS score at 52 weeks, against the predicted 10 points, and approximately a 5-point advantage on PANSS total score. Clozapine showed a trend towards having less total extrapyramidal side effects ( p = 0.1). Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals ( p < 0.05). Net costs of care varied widely, with a mean of �33,588 in the clozapine group and �28,122 in the new atypical group, not a statistically significant difference. Of these costs, 4.0% and 3.3%, respectively, were dueto antipsychotic drug costs.Background/objective: Despite the high comorbidity of substance misuse and schizophrenia, few large scale British studies have looked at symptom profile and outcome in this population. The aim of this study was to use data on substance use among subjects with schizophrenia collected in a randomised controlled trial, validated for the purpose of this study, to see if there are differences between substance users and non users on a variety of outcome measures. Method: 1. A sample of subjects in the CUtLASS study were interviewed using the SCID to determine whether SCID-diagnosed substance misuse disorders corresponded to substance misuse categories generated in the CUtLASS study from casenote review. 2. Substance users were compared with non users on a variety of outcome measures. Results: 1. Two CUtLASS categories, no substance use and major substance use, could be validated against SCID diagnoses; the third category, minor use, could not be validated. 2. Substance misusers were more likely to be young men. There were no significant differences between users and non users for positive and negative symptoms, quality of life, number of previous hospitalisations, extrapyramidal side effects or medication compliance. Drug users were younger at age of first treatment than non users. Alcohol users had more depressive symptoms than non users. Substance users had more negative attitudes towards prescribed medication, although this effect disappeared when age and gender were controlled for. Non compliance was associated with more severe psychopathology, and a worse quality of life. Conclusion: Substance misuse did not seem to confer the adverse outcomes that previous studies suggest.Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.Background: The subjective experience of patients with schizophrenia, receiving antipsychotic medication has been a neglected research area.Methods: In a randomised controlled trial comparing the impact of new atypical antipsychotic drugs versus clozapine, 67 out of 136 patients with schizophrenia were randomised to receive clozapine. Baseline and 12 week assessments included the PANSS, DAI, and the Kemp Compliance scale.Results: The greater percentage improvement in total PANSS scores in patients randomised to clozapine was statistically significant when compared to the atypical group at 12 weeks (p < 0.05). Patients? subjective rating of their mental health improvement since commencing clozapine treatment correlated significantly with actual percentage improvement in PANSS scores from baseline to week 12 (p < 0.01). Significant correlations were also observed between the patients? subjective rating of their mental health improvement and both DAI score and theg12 PANSS insight item (p < 0.05). In a regression analysis, DAI score at week 12 explained 26% of the variance in patients? subjective rating of mental health improvement with clozapine. Percentage PANSS improvement explained a further 8% of the variance.Conclusion: Patients in an RCT of clozapine versus atypicals were able to subjectively rate their own improved mental health status, validated by objective improvement on the PANSS. This was predicted by drug attitude as measured by the DAI. Subjective reports are a useful and valid outcome measure in drug treatment trials.Background: Conceptually quality of life is a broad term and consists of a sense of well-being, life satisfaction and access to resources and opportunities.Methods: A subjective quality of life measure, the Lancashire quality of life scale(Oliver, 1991) was compared with an objective measure, the Heinrichs quality of life scale (Heinrichs et al,1884) in 75 subjects entering a randomised controlled trial comparing conventional and new atypical antipsychotics and clozapine.Results: A significant correlation was found between the two scales (r = 0.386 p < 0.01). Determinants of subjective and objective quality of life were explored using multiple regression analyses. The main determinants of subjective quality of life were depression measured on the Calgary Scale, insight(Birchwood Scale) and nonneurological side-effects, which together explained 44% of the variance p < 0.01. Depression was responsible for 34% of this variance. In contrast, the main determinant of objective QLS were PANSS negative score and PANSS total score. These two together explained 51% of the variance with PANSS negative accounting for most 46% of this p < 0.01.Conclusion: The choice of subjective or objective quality of life measures is likely to reflect different dimensions of outcome,reflecting the underlying psychopathology of schizophrenia as opposed to measuring a discrete construct. A value judgement must therefore be made as to which of these measures best encapsulates what is meant by quality of life in schizophrenic illnesses.Edited by Glen Van Brummelen The purpose of this department is to give sufficient information about the subject matter of each publication to enable users to decide whether to read it. It is our intention to cover all books, articles, and other materials in the field. Books for abstracting and eventual review should be sent to this department. Materials should be sent to Glen Van Brummelen, Bennington College, Bennington, VT 05201, U.S.A. (E-mail: gvanbrum@bennington.edu) Readers are invited to send reprints, autoabstracts, corrections, additions, and notices of publications that have been overlooked. Be sure to include complete bibliographic information, as well as transliteration and translation for non-European languages. We need volunteers willing to cover one or more journals for this department. In order to facilitate reference and indexing, entries are given abstract numbers which appear at the end following the symbol #. A triple numbering system is used: the first number indicates the volume, the second the issue number, and the third the sequential number within that issue. For example, the abstracts for Volume 20, Number 1, are numbered: 20.1.1, 20.1.2, 20.1.3, etc. For reviews and abstracts published in Volumes 1 through 13 there are an author index in Volume 13, Number 4, and a subject index in Volume 14, Number 1. The initials in parentheses at the end of an entry indicate the abstractor. In this issue there are abstracts by Francine Abeles (Kean, NJ), Peter Bernhard (Erlangen, Germany), Herbert Kasube (Peoria, IL), Gary S. Stoudt (Indiana, PA), Kevin VanderMeulen (Hamilton, Canada), David Wallace (Glasgow, UK), and Glen Van Brummelen. Abgrall, Philippe. La Géométrie de l’Astrolabe au Xe Siècle, Arabic Sciences and Philosophy 10(1) (2000), 7–77. An analysis of treatises of al-Saganı̄, al-Qūhı̄, and Ibn Sahl dealing with the projection of the sphere on a plane applied to the construction of the astrolabe. See the review by Emilia Calvo in Mathematical Reviews 2001d:01005. (GSS) #28.4.1 Abraham, George. See #28.4.58. Abramovich, Y. A.; and Veksler, A. I. G. Ya. Lozanovsky: His Contributions to the Theory of Banach Lattices, in Henryk Hudzik and Leszek Skrzypczak, eds., Function Spaces, New York: Dekker, 2000, pp. 5–21. This description of Lozanovsky’s main results in the theory of Banach lattices also contains reflections on his personality and mathematical legacy, as well as a supplement to the papers listed in his obituary. (GVB) #28.4.2 Almgren, Frederick J., Jr. Selected Works of Frederick J. Almgren, Jr., edited by Jean E. Taylor, Providence, RI: American Mathematical Society, 1999, xlvi+586 pp.,

Randomised controlled trial of effect on quality of life of prescription of second generation (atypical) versus first generation antipsychotic drugs in schizophrenia

105. This book contains a collection of the most significant “short” papers and expository and survey articles written by Frederick J. Almgren, Jr. See the review by Giandomenico Orlandi in Mathematical Reviews 2001f:01053. (HEK) #28.4.3 Amunategui, Godofredo Iommi. See #28.4.87. Andreozzi, Luciano. Vito Volterra as Scientific Organizer and the Origins of Mathematical Biology in Italy [in Italian], Nuncius 15(1) (2000), 79–109. Discusses Volterra’s organizational role in oceanographic studies from 1910 to 1925. (GVB) #28.4.4 Aouad, Maroun. See #28.4.61. Apostol, Tom M. A Centennial History of the Prime Number Theorem, in R. P. Bambah, V. C. Dumir, and R. J. Hans-Gill, eds., Number Theory, Basel: Birkhäuser, 2000, pp. 1–14. A survey article on the prime number 315 0315-0860/01

Randomised controlled trial of effect on quality of life of prescription of second generation (atypical) versus first generation antipsychotic drugs in schizophrenia [Abstract]. 20th International Congress on Schizophrenia Research, Savannah, Georgia, US.

35.00 C

Practicalities of running non-commercial clinical drug trials in the NHS: A resource based on the experiences of the CUtLASS study (Cost utility of the latest antipsychotics in severe schizophrenia)

This is the Special Issue: Abstracts of the 20th International Congress on Schizophrenia Research 2005This journal issue entitled: Special Issue: Abstracts of the XX International Congress on Schizophrenia Research

Substance misuse in schizophrenia: does it affect compliance and other outcome measures? [Abstract]. 12th Biennial Winter Workshop on Schizophrenia, Davos, Switzerland.

This is the Special Issue: Abstracts of the 20th International Congress on Schizophrenia Research 2005This journal issue entitled: Special Issue: Abstracts of the XX International Congress on Schizophrenia Research

Substance misuse in schizophrenia: does it affect compliance and other outcome measures?

Background: Despite randomized controlled trials (RCTs) being regarded as the gold standard for intervention research in mental health, there is a lack of guidance on the practicalities of setting up and conducting such trials in the NHS. Aims: To provide information for new clinical trials collated from the experiences of carrying out the NCCHTA-funded CUtLASS trial (reported in an HTA Monograph entitled “Randomised controlled trials of conventional versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment”). Conclusions: The main practical considerations in clinical trials can be grouped into issues of Staffing, Trial Management and Data Management. Matters that impact on recruitment include the research question, the interest of clinicians in that question, the extent of clinical equipoise, and the provision of adequate reimbursement of service support costs associated with participation in the trial.

Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1)

Background: A single-blind, multicentre RCT compared the class of new (non-clozapine) atypical drugs with clozapine in patients in the NHS whose medication was being changed because of poor clinical response to two or more antipsychoticdrugs.Methods: The primary outcome was the Quality of Life Scale. Secondary clinical outcomes included symptoms (PANSS), side effects and participant satisfaction. Economic outcomes were costs of health and social care and a utility measure. A total of 136 (98% of the planned sample) participants were randomised. Followup at 52 weeks, blind to treatment allocation, was complete in 87%.Results: The intent to treat comparison of new atypicals compared with clozapine in people with more narrowly defined treatment resistance showed an advantage for commencing clozapine in quality of life (QLS) at trend level ( p = 0.08) and insymptoms (PANSS), that was statistically significant ( p = 0.01), at 1 year. Clozapine showed approximately a 4-point advantage (not statistically significant) on QLS score at 52 weeks, against the predicted 10 points, and approximately a 5-point advantage on PANSS total score. Clozapine showed a trend towards having less total extrapyramidal side effects ( p = 0.1). Participants reported at 12 weeks that their mental health was significantly better with clozapine than with new atypicals ( p < 0.05). Net costs of care varied widely, with a mean of �33,588 in the clozapine group and �28,122 in the new atypical group, not a statistically significant difference. Of these costs, 4.0% and 3.3%, respectively, were dueto antipsychotic drug costs.Background/objective: Despite the high comorbidity of substance misuse and schizophrenia, few large scale British studies have looked at symptom profile and outcome in this population. The aim of this study was to use data on substance use among subjects with schizophrenia collected in a randomised controlled trial, validated for the purpose of this study, to see if there are differences between substance users and non users on a variety of outcome measures. Method: 1. A sample of subjects in the CUtLASS study were interviewed using the SCID to determine whether SCID-diagnosed substance misuse disorders corresponded to substance misuse categories generated in the CUtLASS study from casenote review. 2. Substance users were compared with non users on a variety of outcome measures. Results: 1. Two CUtLASS categories, no substance use and major substance use, could be validated against SCID diagnoses; the third category, minor use, could not be validated. 2. Substance misusers were more likely to be young men. There were no significant differences between users and non users for positive and negative symptoms, quality of life, number of previous hospitalisations, extrapyramidal side effects or medication compliance. Drug users were younger at age of first treatment than non users. Alcohol users had more depressive symptoms than non users. Substance users had more negative attitudes towards prescribed medication, although this effect disappeared when age and gender were controlled for. Non compliance was associated with more severe psychopathology, and a worse quality of life. Conclusion: Substance misuse did not seem to confer the adverse outcomes that previous studies suggest.Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.Background/objective: There is accumulating evidence for an important role for vitamin D in brain function, including our recent observations that animals deprived of vitamin D in utero had brains that were altered in shape at birth, with increased cell proliferation and reduced levels of NGF and GDNF. In the current study we examined the hypothesis that vitamin D deficiency during two separate developmental periods alters adult behaviour. Methods: Rats were conceived and born to mothers receiving a vitamin D-deficient diet and housed without UV light. At birth, the litters were reduced to three males and three females and half the mothers were placed under normal vitamin D conditions whilst half remained under vitamin D deplete conditions. At weaning, all animals were fed the normal diet. Mothers, and all animals at weaning, were rendered normocalcaemic with calcium supplemented water (2 mM). Control animals were born to mothers fed a normal diet but subject to similar litter size and calcium supplementation. At 10 weeks, all animals were subject to the holeboard test, elevated plus maze test, social interaction, prepulse inhibition of the acoustic startle response and a forced swim test. Results: Early vitamin D deficiency selectively enhanced locomotion in the holeboard test and increased activity in the elevated plus maze. Thus, early vitamin D deficiency appeared to induce quite specific behavioural deficits in adulthood, without inducing severe learning or motor abnormalities. Conclusion: These observations are consistent with an increase in dopaminergic tone, a finding previously reported in vitamin D depleted animals.Background: The subjective experience of patients with schizophrenia, receiving antipsychotic medication has been a neglected research area.Methods: In a randomised controlled trial comparing the impact of new atypical antipsychotic drugs versus clozapine, 67 out of 136 patients with schizophrenia were randomised to receive clozapine. Baseline and 12 week assessments included the PANSS, DAI, and the Kemp Compliance scale.Results: The greater percentage improvement in total PANSS scores in patients randomised to clozapine was statistically significant when compared to the atypical group at 12 weeks (p < 0.05). Patients? subjective rating of their mental health improvement since commencing clozapine treatment correlated significantly with actual percentage improvement in PANSS scores from baseline to week 12 (p < 0.01). Significant correlations were also observed between the patients? subjective rating of their mental health improvement and both DAI score and theg12 PANSS insight item (p < 0.05). In a regression analysis, DAI score at week 12 explained 26% of the variance in patients? subjective rating of mental health improvement with clozapine. Percentage PANSS improvement explained a further 8% of the variance.Conclusion: Patients in an RCT of clozapine versus atypicals were able to subjectively rate their own improved mental health status, validated by objective improvement on the PANSS. This was predicted by drug attitude as measured by the DAI. Subjective reports are a useful and valid outcome measure in drug treatment trials.Background: Conceptually quality of life is a broad term and consists of a sense of well-being, life satisfaction and access to resources and opportunities.Methods: A subjective quality of life measure, the Lancashire quality of life scale(Oliver, 1991) was compared with an objective measure, the Heinrichs quality of life scale (Heinrichs et al,1884) in 75 subjects entering a randomised controlled trial comparing conventional and new atypical antipsychotics and clozapine.Results: A significant correlation was found between the two scales (r = 0.386 p < 0.01). Determinants of subjective and objective quality of life were explored using multiple regression analyses. The main determinants of subjective quality of life were depression measured on the Calgary Scale, insight(Birchwood Scale) and nonneurological side-effects, which together explained 44% of the variance p < 0.01. Depression was responsible for 34% of this variance. In contrast, the main determinant of objective QLS were PANSS negative score and PANSS total score. These two together explained 51% of the variance with PANSS negative accounting for most 46% of this p < 0.01.Conclusion: The choice of subjective or objective quality of life measures is likely to reflect different dimensions of outcome,reflecting the underlying psychopathology of schizophrenia as opposed to measuring a discrete construct. A value judgement must therefore be made as to which of these measures best encapsulates what is meant by quality of life in schizophrenic illnesses.Edited by Glen Van Brummelen The purpose of this department is to give sufficient information about the subject matter of each publication to enable users to decide whether to read it. It is our intention to cover all books, articles, and other materials in the field. Books for abstracting and eventual review should be sent to this department. Materials should be sent to Glen Van Brummelen, Bennington College, Bennington, VT 05201, U.S.A. (E-mail: gvanbrum@bennington.edu) Readers are invited to send reprints, autoabstracts, corrections, additions, and notices of publications that have been overlooked. Be sure to include complete bibliographic information, as well as transliteration and translation for non-European languages. We need volunteers willing to cover one or more journals for this department. In order to facilitate reference and indexing, entries are given abstract numbers which appear at the end following the symbol #. A triple numbering system is used: the first number indicates the volume, the second the issue number, and the third the sequential number within that issue. For example, the abstracts for Volume 20, Number 1, are numbered: 20.1.1, 20.1.2, 20.1.3, etc. For reviews and abstracts published in Volumes 1 through 13 there are an author index in Volume 13, Number 4, and a subject index in Volume 14, Number 1. The initials in parentheses at the end of an entry indicate the abstractor. In this issue there are abstracts by Francine Abeles (Kean, NJ), Peter Bernhard (Erlangen, Germany), Herbert Kasube (Peoria, IL), Gary S. Stoudt (Indiana, PA), Kevin VanderMeulen (Hamilton, Canada), David Wallace (Glasgow, UK), and Glen Van Brummelen. Abgrall, Philippe. La Géométrie de l’Astrolabe au Xe Siècle, Arabic Sciences and Philosophy 10(1) (2000), 7–77. An analysis of treatises of al-Saganı̄, al-Qūhı̄, and Ibn Sahl dealing with the projection of the sphere on a plane applied to the construction of the astrolabe. See the review by Emilia Calvo in Mathematical Reviews 2001d:01005. (GSS) #28.4.1 Abraham, George. See #28.4.58. Abramovich, Y. A.; and Veksler, A. I. G. Ya. Lozanovsky: His Contributions to the Theory of Banach Lattices, in Henryk Hudzik and Leszek Skrzypczak, eds., Function Spaces, New York: Dekker, 2000, pp. 5–21. This description of Lozanovsky’s main results in the theory of Banach lattices also contains reflections on his personality and mathematical legacy, as well as a supplement to the papers listed in his obituary. (GVB) #28.4.2 Almgren, Frederick J., Jr. Selected Works of Frederick J. Almgren, Jr., edited by Jean E. Taylor, Providence, RI: American Mathematical Society, 1999, xlvi+586 pp.,

Randomized Controlled Trial of Effect of Prescription of Clozapine Versus Other Second-Generation Antipsychotic Drugs in Resistant Schizophrenia

105. This book contains a collection of the most significant “short” papers and expository and survey articles written by Frederick J. Almgren, Jr. See the review by Giandomenico Orlandi in Mathematical Reviews 2001f:01053. (HEK) #28.4.3 Amunategui, Godofredo Iommi. See #28.4.87. Andreozzi, Luciano. Vito Volterra as Scientific Organizer and the Origins of Mathematical Biology in Italy [in Italian], Nuncius 15(1) (2000), 79–109. Discusses Volterra’s organizational role in oceanographic studies from 1910 to 1925. (GVB) #28.4.4 Aouad, Maroun. See #28.4.61. Apostol, Tom M. A Centennial History of the Prime Number Theorem, in R. P. Bambah, V. C. Dumir, and R. J. Hans-Gill, eds., Number Theory, Basel: Birkhäuser, 2000, pp. 1–14. A survey article on the prime number 315 0315-0860/01