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David Healy

Publications and source records attributed to David Healy.

At least 19 recordsLinked to original sources
PubMed2006

Three-dimensional brittle shear fracturing by tensile crack interaction.

Faults in brittle rock are shear fractures formed through the interaction and coalescence of many tensile microcracks. The geometry of these microcracks and their surrounding elastic stress fields control the orientation of the final shear fracture surfaces. The classic Coulomb-Mohr failure criterion predicts the development of two conjugate (bimodal) shear planes that are inclined at an acute angle to the axis of maximum compressive stress. This criterion, however, is incapable of explaining the three-dimensional polymodal fault patterns that are widely observed in rocks. Here we show that the elastic stress around tensile microcracks in three dimensions promotes a mutual interaction that produces brittle shear planes oriented obliquely to the remote principal stresses, and can therefore account for observed polymodal fault patterns. Our microcrack interaction model is based on the three-dimensional solution of Eshelby, unlike previous models that employed two-dimensional approximations. Our model predicts that shear fractures formed by the coalescence of interacting mode I cracks will be inclined at a maximum of 26 degrees to the axes of remote maximum and intermediate compression. An improved understanding of brittle shear failure in three dimensions has important implications for earthquake seismology and rock-mass stability, as well as fluid migration in fractured rocks.

Journal Article↗
PubMed2006

Manufacturing consensus.

The Food and Drug Administration (FDA) has declared that it would be illegal to advertise as or in any way claim your drug to be superior to competitors on the market, which are up to 30 times cheaper. How does a pharmaceutical company market such a product? The answer is to enlist academics to form expert panels to construct guidelines and algorithms, or participate in Delphi panels and other exercises, which can be expected to prove that newer, more costly drugs produce cost savings. These academics do so on the basis of the existing clinical trial evidence--which supposedly the FDA has used to come to its verdict that the newer compound is no better than its competitors. However, where the FDA has seen the raw data, academics later see the published data. In between intervenes a medical writing exercise, which produces the first and most important piece of advertising for any pharmaceutical product--the randomized controlled trial infomercial. This paper explores how pharmaceutical companies manufacture an apparent academic consensus and, in so doing, gives a case study of the recent controversies surrounding the marketing of selective serotonin reuptake inhibitor (SSRI) drugs for adolescent depression.

Adolescent↗
PubMed2005

A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients.

BACKGROUND: This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol. METHODS: A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt). RESULTS: In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P < or = 0.001), there was a slower start of follicular growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4; P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU; P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively; not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively; not significant). CONCLUSION: OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen.

Adolescent↗
PubMed2005

The acetochlor registration partnership surface water monitoring program for four corn herbicides.

A surface drinking water monitoring program for four corn (Zea mays L.) herbicides was conducted during 1995-2001. Stratified random sampling was used to select 175 community water systems (CWSs) within a 12-state area, with an emphasis on the most vulnerable sites, based on corn intensity and watershed size. Finished drinking water was monitored at all sites, and raw water was monitored at many sites using activated carbon, which was shown capable of removing herbicides and their degradates from drinking water. Samples were collected biweekly from mid-March through the end of August, and twice during the off-season. The analytical method had a detection limit of 0.05 microg L(-1) for alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide] and 0.03 microg L(-1) for acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide], atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl)-acetamide]. Of the 16528 drinking water samples analyzed, acetochlor, alachlor, atrazine, and metolachlor were detected in 19, 7, 87, and 53% of the samples, respectively. During 1999-2001, samples were also analyzed for the presence of six major degradates of the chloroacetanilide herbicides, which were detected more frequently than their parent compounds, despite having higher detection limits of 0.1 to 0.2 microg L(-1). Overall detection frequencies were correlated with product use and environmental fate characteristics. Reservoirs were particularly vulnerable to atrazine, which exceeded its 3 microg L(-1) maximum contaminant level at 25 such sites during 1995-1999. Acetochlor annualized mean concentrations (AMCs) did not exceed its mitigation trigger (2 microg L(-1)) at any site, and comparisons of observed levels with standard measures of human and ecological hazards indicate that it poses no significant risk to human health or the environment.

Agriculture↗
PubMed2005

Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials.

OBJECTIVE: To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Medline and the Cochrane Collaboration's register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group. SELECTION OF STUDIES: Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week. RESULTS: Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42). DISCUSSION: Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.

Adult↗
PubMed2005

Spectroscopic and optimization modeling study of nitrous acid in aqueous solution.

Nitrous acid (HONO) and the nitrite ion represent a particularly important conjugate pair of trace species with regard to heterogeneous behavior within the bulk, and on the surface, of aqueous atmospheric dispersions: this role results from their chemical reactivity, photolysis pathways, solubility, and ambient concentration levels. The actual ratio of NO(2)(-): HONO in solution is determined by the pH and the nitrous acid dissociation constant (pK(a)) which is generally quoted in the literature as 3.27 at 298 K. However there is much disagreement in published works as to the exact value, which should be used in model calculations relevant to the atmosphere. Furthermore even though the nitrite ion is known to absorb solar radiation in the 300-400 nm region and represents a dominant source of *OH radicals in surface seawater, large variations in the measured molar decadic absorption coefficients, epsilon, for nitrite ions (and aqueous HONO) are evident in the literature. In the current study, using a UV-vis spectrometric approach with careful baseline subtraction, the relevant epsilon values for the nitrite ion were determined to be 8.16 +/- 0.08 M(-1) cm(-1) for the npi transitions at 290 nm and 22.1 +/- 0.22 M(-1) cm(-1) at 354 nm. For HONO, the wavelength maximum for the strongest vibronic band in solution was found at 372 nm with an epsilon value of 60.52 +/- 0.6 M(-1) cm(-1). Using the Henderson-Hasselbalch equation and the above data, a value of 2.8 +/- 0.1 is therefore reported here for the pK(a) of nitrous acid. A Newton-Gauss method was then employed to solve a set of nonlinear equations defining the chemical speciation model for HONO in solution using an algorithm written in FORTRAN 90. A model based on a simple one-step protonation worked well for intermediate pHs (6-3) but departed from the experimental observations in highly acidic media. A two-step equilibrium model involving the nitroacidium ion, H(2)ONO(+), gave a much closer fit in the very acidic region, while having little or no effect on the pH 6-3 section of the profile.

Journal Article↗
PubMed2005

Attitudes toward antipsychotic medication: the impact of clinical variables and relationships with health professionals.

CONTEXT: Nonadherence to antipsychotic medication is a major cause of psychotic relapse and is strongly influenced by attitudes toward treatment. Although patient variables such as insight and symptoms that contribute toward attitudes have been identified, the contributions of relationship and service factors have not been adequately studied. OBJECTIVE: To determine relations between clinical and service variables and attitudes toward medication in people with a diagnosis of schizophrenia and schizoaffective disorder. DESIGN: Consecutively admitted patients were approached to take part; 23 refused. Measures included symptoms, insight, drug adverse effects, self-reported adherence, attitudes toward treatment, perceived relationship with the prescriber, ward atmosphere, and admission experience. Data were analyzed by a proportional odds model and structural equation modeling to test predicted paths between experience of admission, relationship variables, attitudes toward treatment, and self-reported adherence to medication. SETTING: Twenty-eight inpatient wards at 8 hospitals in North Wales and the Northwest of England. Sites included hospitals with inner-city and rural catchment areas. Patients Two hundred twenty-eight patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder, assessed during acute admission. MAIN OUTCOME MEASURES: Attitudes toward treatment and self-reported adherence to medication. RESULTS: The data fit a model in which attitudes toward treatment were predicted by insight, relationship with staff (especially the physician-prescriber), and the patient's admission experience (maximum likelihood chi(2)(49) = 89.3, P<.001). A poor relationship with the prescriber, experience of coercion during admission, and low insight predicted a negative attitude toward treatment. CONCLUSIONS: The quality of relationships with clinicians during acute admission appears to be an important determinant of patients' attitudes toward treatment and adherence to medication. Enhancing such relationships may yield important clinical benefits.

Adolescent↗
PubMed2005

Presentation and frequency of catatonia in new admissions to two acute psychiatric admission units in India and Wales.

BACKGROUND: There are no modern cross-cultural comparative studies of the frequency and clinical presentation of catatonia in a Western country and India using standardized rating instruments and diagnostic criteria. METHOD: A total of 104 consecutively admitted patients in Wales and in India were screened for catatonic features using the same standardized rating instrument by the same psychiatrist to generate DSM-IV and other diagnostic criteria for catatonia, and a profile of signs in catatonia. Inter-rater reliability for the ratings made by the research psychiatrist was established with local psychiatrists at each unit. RESULTS: The frequency of DSM-IV criteria catatonia was 13.5% in India versus 9.6% in Wales ( N . S .). The severity of catatonia did not differ between the two units. However, retarded catatonia was more common in India (12.5%) versus Wales ( p <0.05) whereas the frequency of excited catatonia was equally common in both units. Catatonia was found in many different mental disorders not just schizophrenia and affective disorder. CONCLUSIONS: Catatonia is commonly found among psychiatric in-patients with a similar frequency and severity but differing clinical presentations in Wales and India. Some classic signs of catatonia like posturing, catalepsy, staring and stupor were more frequent among psychiatric admissions in India than Wales. The differing clinical presentations may be due to differences in demographic features rather than cultural or aetiological factors.

Catatonia↗
PubMed2005

Antidepressant drug use & the risk of suicide.

There have been longstanding concerns about the propensity of antidepressants to precipitate suicidality in vulnerable individuals. To investigate this further, first we have analyzed all clinical trials, and in particular trials submitted to regulators for evidence on the relative risk of antidepressants versus placebo for this hazard. Second, we have compiled current epidemiological evidence germane to the issue. Third, we have constructed a model (Investigative Medication Routine; IMR) to shed light on the interactions between drug uptake, patient numbers on treatment and suicidal events. The clinical trial data gives rise to a relative risk of suicide on antidepressants over placebo of the order of a 2.0-2.5 times greater risk with treatment. These figures are supported by epidemiological findings. Investigative Medication Routine translates such findings into estimates of likely adverse outcomes, and explains why apparently increasing consumption of antidepressants would not be expected to lead to increased national suicide rates. From this data, we conclude that there is a clear signal that suicides and suicidal acts may be linked to antidepressant usage. It would seem likely that explicit warnings and monitoring in the early stages of treatment could greatly minimize these hazards.

Antidepressive Agents↗
PubMed2005

A randomised trial of surgical, medical and expectant management of first trimester spontaneous miscarriage.

BACKGROUND: Medical management and expectant care have been considered possible alternatives to surgical evacuation of the uterus for first trimester spontaneous miscarriage in recent years. AIM: To compare the effectiveness and safety of medical and expectant management with surgical management for first trimester incomplete or inevitable miscarriage. METHODS: Forty women were recruited following diagnosis of incomplete or inevitable miscarriage, and randomised to surgical, medical or expectant care via an off-site, computerised enrollment system. The primary outcome was the effectiveness of medical (vaginal misoprostol) and expectant management relative to surgical evacuation, assessed at 10-14 days and 8 weeks post-recruitment. Infection, pain, bleeding, anxiety, depression, physical and emotional recovery were assessed also. Analysis was by intention-to-treat. RESULTS: Effectiveness at 8 weeks was lower for medical (80.0%) and expectant (78.6%) than for surgical management (100.0%). Two women in the medical group had confirmed infections. Bleeding lasted longer in the expectant group than in the surgical group. There were no significant differences in pain, physical recovery, anxiety or depression between the groups. 54.6%, 42.9% and 57.1% of the surgical, medical and expectant groups respectively would opt for the same treatment again. CONCLUSION: Expectant care appears to be sufficiently safe and effective to be offered as an option for women. Medical management might carry a higher risk of infection than surgical or expectant care.

Abortifacient Agents, Nonsteroidal↗
PubMed2005

Service utilization in 1896 and 1996: morbidity and mortality data from North Wales.

The 1896 and 1996 populations of North-West Wales are similar in number, ethnic and social mix and rurality, enabling a study of the comparative prevalence of service utilization, as well as the morbidity and mortality associated with mental illness in 1894-96 and 1996. The 1996 data reveal a 15 times greater prevalence of admissions for all diagnoses, and three times greater prevalence of admissions by detention, compared with 1896. Patients now spend more time in a service bed than they did 100 years ago. Death as a direct consequence of mental illness is commoner now than 100 years ago. There is therefore a major disjunction between the rhetoric and the reality of mental health service utilization. General factors related to changing health care and expectations and specific factors linked to the mental health appear to have led to an increased rate of service utilization in the modern period.

Bed Occupancy↗
PubMed2005

The impact of mood stabilizers on bipolar disorder: the 1890s and 1990s compared.

This study comparing patterns of service utilization by bipolar patients in North-West Wales found a greater prevalence of service utilization in the 1990s compared with the 1890s. In the pre-lithium era, admissions for bipolar disorders occurred at a rate of 4 every 10 years; they now occur at a rate of 6.3 every 10 years. Where 100 years ago, there were 16 bipolar patients per million population resident per day in hospital, there are now 24 per million resident in acute service beds and more in non-acute beds. These data are incompatible with simple claims that mood stabilizing drugs 'work'. An alternative is that these agents have treatment effects, and further research is needed to match treatments to patients in order to optimize outcomes.

Antimanic Agents↗