Are block copolymer worms more effective Pickering emulsifiers than block copolymer spheres?

RAFT-mediated polymerisation-induced self-assembly (PISA) is used to prepare six types of amphiphilic block copolymer nanoparticles which were subsequently evaluated as putative Pickering emulsifiers for the stabilisation of n-dodecane-in-water emulsions. It was found that linear poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (PGMA-PHPMA) diblock copolymer spheres and worms do not survive the high shear homogenisation conditions used for emulsification. Stable emulsions are obtained, but the copolymer acts as a polymeric surfactant; individual chains rather than particles are adsorbed at the oil-water interface. Particle dissociation during emulsification is attributed to the weakly hydrophobic character of the PHPMA block. Covalent stabilisation of these copolymer spheres or worms can be readily achieved by addition of ethylene glycol dimethacrylate (EGDMA) during the PISA synthesis. TEM studies confirm that the resulting cross-linked spherical or worm-like nanoparticles survive emulsification and produce genuine Pickering emulsions. Alternatively, stabilisation can be achieved by either replacing or supplementing the PHPMA block with the more hydrophobic poly(benzyl methacrylate) (PBzMA). The resulting linear spheres or worms also survive emulsification and produce stable n-dodecane-in-water Pickering emulsions. The intrinsic advantages of anisotropic worms over isotropic spheres for the preparation of Pickering emulsions are highlighted. The former particles are more strongly adsorbed at similar efficiencies compared to spheres and also enable smaller oil droplets to be produced for a given copolymer concentration. The scalable nature of PISA formulations augurs well for potential applications of anisotropic block copolymer nanoparticles as Pickering emulsifiers.

The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection.

BACKGROUND/AIMS: The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection. METHODS: The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations. RESULTS: The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%. CONCLUSIONS: A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.

A comparison of the Composite International Diagnostic Interview (CIDI-Auto) with clinical assessment in diagnosing mood and anxiety disorders.

OBJECTIVE: Increasingly, epidemiological studies are employing computerized and highly standardized interviews, such as the Composite International Diagnostic Interview (CIDI-Auto), to assess the prevalence of psychiatric illness. Recent studies conducted in specialist units have reported poor agreement between experienced clinicians' and CIDI-Auto diagnoses. In this study we investigated the concordance rate between clinicians and the CIDI-Auto for the diagnosis of six anxiety disorders and two mood disorders, whereby the CIDI-Auto was treated as the 'gold standard'. METHOD: Subjects were 262 patients who were assessed by a clinical psychologist or psychiatrist and completed the CIDI-Auto at a tertiary referral unit for anxiety and mood disorders. Agreement between the clinicians' diagnoses and the diagnoses generated by the CIDI-Auto according to both DSM-IV and ICD-10 codes, were examined by kappa statistics. Sensitivity and specificity values were also calculated. RESULTS: Agreement between clinicians and the CIDI-Auto (DSM-IV) ranged from poor for social phobia and posttraumatic stress disorder (kappa < 0.30) to moderate for obsessive- compulsive disorder (OCD; kappa = 0.52). Agreement between clinicians and the CIDI-Auto (ICD-10) ranged from poor for major depressive episode (kappa = 0.25) to moderate for OCD (kappa = 0.57). With the CIDI diagnosis treated as the gold standard, clinicians' diagnoses showed low sensitivity (kappa < 0.70) for all the disorders except for OCD (for ICD-10), but high specificity (kappa > 0.70) for all the disorders. CONCLUSION: Poor agreements between experienced clinicians and the CIDI-Auto were reported for anxiety and mood disorders in the current study. A major implication is that if diagnosis alone directed treatment, then patients could receive different treatments, depending on whether the computer, or a clinician, made the diagnosis.

Improving access for rural Australians to treatment for anxiety and depression: The University of Melbourne Depression and Anxiety Research and Treatment Group-Bendigo Health Care Group initiative.

Rural Australians have limited access to care for mental health problems. We describe a collaboration between the University of Melbourne Departments of Psychology and Psychiatry and a rural Area Mental Health Service to provide a specialist anxiety and depression treatment service in rural Victoria. The clinical service and the education and training approach are described.

A comparative study of venlafaxine with a focused education and psychotherapy program versus venlafaxine alone in the treatment of depression in general practice.

The efficacy of a focused education and psychotherapy program (FEPP) plus antidepressant was compared with that of usual psychosocial treatment and antidepressant in a general practice setting. The FEPP comprised interpersonal counselling (IPC) delivered in a modified way to suit the general practice setting, together with patient education and selected cognitive behavioural techniques. All patients were treated with venlafaxine-XR. Thirty-one patients entered the study, three withdrawing before completion of the 12 week trial. Both treatments produced a statistically significant reduction in BDI and POMS scores from baseline, with greater improvement evident in the FEPP plus antidepressant group. Copyright 2001 John Wiley & Sons, Ltd.

Depressive symptoms reduced in individuals with HIV/AIDS treated with highly active antiretroviral therapy: a longitudinal study.

OBJECTIVE: The aims of this study were to investigate the stability of depressive symptoms over time, explore possible reasons for the genesis of depressive symptoms, examine psychosocial adjustment over time and examine the effects of the introduction of highly active antiretroviral therapy (HAART) in a group of HIV infected patients. METHOD: HIV seropositive outpatients were assessed at 6 monthly intervals over a 2-year period. At each assessment patients completed the Beck Depression Inventory, the Life Event Inventory, the Core Bereavement Item questionnaire and the Psychosocial Adjustment to Illness Scale. Details regarding HIV illness progression and antiretroviral treatment were recorded for each follow-up assessment. RESULTS: One hundred and sixty-three patients completed the baseline assessment and proceeded to the 2-year follow-up study. Most patients remained well over the 2-year follow-up period; mean CD4 count for the group increased over the study period. Ten patients developed AIDS and 18 patients died. Antiretroviral medications changed significantly during the follow-up, with most patients changing to combination (triple) therapy, which included the use of a protease inhibitor. Psychosocial stressors (life event distress and number of bereavements) reduced as the study progressed. Reported depressive symptoms decreased over time and psychosocial adjustment to illness tended to improve over the 2-year period. CONCLUSIONS: Over a 2-year follow-up period HIV/AIDS symptoms and illness markers and psychosocial adjustment to illness improved, psychological stressors and depressive symptoms decreased, with a temporal relationship to changes in antiretroviral therapy.

Secondary mania in patients with HIV infection: are antiretrovirals protective?

A case-control study of 19 patients with HIV-associated mania and 57 HIV-seropositive control patients matched by CD4 cell count, age, and year of treatment was undertaken to investigate associations with risk factors for human immunodeficiency virus (HIV) infection, treatment, and disease. There was no significant difference between groups for HIV exposure category, baseline health status, or drugs other than antiretrovirals. Zidovudine therapy provided a significant protective effect against the development of mania, whether administered at or prior to diagnosis of mania. In a 3-year follow-up study, incident AIDS dementia was significantly more common in patients with mania, despite no apparent difference in survival between cases and controls. These findings strengthen the evidence of an etiological association of HIV neuropathology with AIDS mania by demonstrating a protective effect of an antiretroviral agent able to penetrate the central nervous system.

The evaluation of depression in inpatients with HIV disease.

OBJECTIVES: The aim of this paper is: to compare the utility of four approaches to the diagnosis of depression in patients with human immunodeficiency virus (HIV) disease; to examine the utility of four rating scales to assess the presence and severity of depression; and to devise a set of substitutive criteria that would be appropriate in patients with HIV disease. METHOD: A group of inpatients was assessed using standard clinical interview. Patients found to have major depression using DSM-III-R (aetiological) criteria were assessed using inclusive, substitutive and exclusive criteria for the diagnosis of depression. Severity was assessed using the Hamilton Depression Rating Scale (HDRS), the Montgomery Asberg Depression Rating Scale (MADRS), the Beck Depression Inventory (BDI), and the Centre for Epidemiological Studies Depression Rating Scale (CES-D). A group of control patients were matched for age and severity of HIV illness. RESULTS: Seventeen patients met DSM-III-R (aetiological criteria) for major depression. All were male; they had a mean age of 40.6 years and one-third had acquired immune deficiency syndrome (AIDS). Using alternative approaches to the diagnosis of depression, up to five additional 'depressed' patients were identified ('false positives'). All 17 patients meeting the DSM-III-R criteria also met the substitutive and exclusive criteria but only 15 exclusive criteria. Of the 17 controls (not meeting DSM-III-R criteria), two met substitutive, five inclusive and one exclusive criteria for depression. The mean (+/- SD) scores for the patients and controls were significantly different on all four rating scales. Analysis of individual items on the rating scales revealed that a number did not show significant differences between the depressed and nondepressed groups: on the MADRS the items lassitude and inner tension; on the HDRS the three items depicting anxiety symptoms, loss of libido, hypochondriasis, loss of weight, and maintenance of insight; on the BDI a sense of being punished, disappointed in self, being self-critical, a feeling of looking unattractive, fatigue, weight loss, worried about health and loss of libido; on the CES-D I felt just as good as others, hopeful, talk less, people unfriendly and felt people dislike me. CONCLUSIONS: The aetiological approach used by clinicians familiar with the features of HIV disease, was found to be useful. All four rating scales differentiated equally well between depressed and non-depressed groups.

Secondary mania in patients with HIV infection.

OBJECTIVE: The aim of this study was to identify a cohort of patients with mania secondary to HIV infection, to describe the clinical and radiological features of HIV-related mania, and to describe the treatment outcome of the patients. METHOD: All patients referred to the HIV consultation-liaison psychiatry service over the 29-month period from January 1993 to June 1995 were screened for the presence of manic symptoms. Diagnosis of mania was made according to DSM-III-R. Cases were defined as secondary mania if there was no clear history of mood disorder, and no family history of mood disorder. Cases were interviewed by the treating psychiatry registrar and psychiatrist to obtain information regarding present and past psychiatric history and family history of psychiatric disorder. The psychiatry registrar and consultant determined treatment. RESULTS: Twenty-three patients with mania were identified; 19 were considered to have secondary mania. The prevalence of secondary mania over the 29 months was 1.2% for HIV-positive patients, and 4.3% for those with AIDS. The clinical characteristics and response to treatment appeared to be similar to mania associated with bipolar affective disorder (primary mania). Neuroradiological abnormalities were common, occurring in 10 of the 19 patients, but did not appear to be clinically relevant. Cognitive impairment developed in five of the 15 patients where follow-up was possible. CONCLUSIONS: Mania occurring in advanced HIV disease appears to be more common than expected from epidemiological data regarding bipolar affective disorder. Differentiating secondary from primary mania has implications for the management and prognosis of mania.

Liaison psychiatry in an HIV/AIDS unit.

OBJECTIVE: To provide an overview of the work of a liaison psychiatry service to an HIV/AIDS inpatient unit, and particularly to examine the identification of mood and related disorders by referring doctors. METHOD: The MICRO-CARES prospective clinical database system was used to obtain data on all patients referred to the HIV/AIDS consultation-liaison psychiatry service in an infectious diseases hospital in Melbourne. RESULTS: Three hundred and ninety-two inpatient referrals were made in the 2 years from 1993-1995: a referral rate of 16.7%. The most frequent reasons for referral were evaluation of coping problems (42%), assessment of possible depression (31%), and assessment of psychotropic medication (24.5%). The most common psychiatric diagnoses were mood disorders (36.5%), psychoactive substance use disorders (22.7%) and organic mental disorders (18.1%). Overall concordance of recognition of depression by the referring doctor and diagnosis of depression by the consultant psychiatrist was 79%; 20% false positive rate, 23% false negative rate. CONCLUSIONS: Psychiatric comorbidity is common in patients with HIV/AIDS. Reasons for referral vary from those seen in other inpatient settings. Previously noted problems such as the misdiagnosis of psychiatric disorder and the mislabelling of the syndrome recognised by psychiatrists as depression were noted here.

The role of a specialist team in implementing continuing health care guidelines in hospitalized patients.

BACKGROUND: Assessment of continuing health care needs is unstandardized and often undertaken by professionals not trained in the management of complex disability. METHODS: A 6 month prospective study to evaluate the role of a specialist team in implementing continuing care guidelines in hospitalized patients. The team was responsible for assessment and facilitation of access to continuing health care throughout the hospital between hospital and community on a non-age-related basis. It had access to six inpatient beds and a budget to purchase health care after discharge for 7 days. Patients with complex disability were referred to the team if their continuing health care needs could not be assessed, improved or provided within routine practice. RESULTS: Of the 93 patients included in the study, 34 (37%) were from geriatric wards and 59 (63%) from other specialties. Twenty-six (44%) of the patients from other specialties had been inappropriately referred (no continuing health care needs) and 24 (41%) appropriate patients had not been referred because of inadequate assessments. It was possible to facilitate discharge and continuing care provision in 26 patients without transfer to dedicated beds. Thirty-two patients were transferred for further management (median length of stay 17 days). Three (9%) patients died, 20 (63%) were discharged home and six (19%) were discharged to institutional care. Three patients had to be transferred to acute care. A high level of satisfaction with support and post-discharge arrangements was reported by 26 (81%) patients, 25 (78%) carers and 26 (81%) general practitioners for patients transferred to specialist beds. CONCLUSIONS: Specialist intervention, using a team approach, facilitates effective implementation of continuing care guidelines in hospitalized patients.

Depressive symptoms in patients with HIV infection: a further exploration.

OBJECTIVE: The aim of this study was to assess the frequency and severity of depressive symptoms, to determine the rate of depressive disorder, to explore possible reasons for the development of depressive symptoms and to examine the effects of depression in a group of human immunodeficiency virus (HIV)-positive patients. METHOD: HIV-positive patients attending an outpatient treatment facility were assessed by the research psychologist and completed a number of questionnaires: the Beck Depression Inventory (BDI); the Life Event Inventory (LEI); the Core Bereavement Item (CBI-17) questionnaire; and the Psychosocial Adjustment to illness Scale (PAIS). Patients scoring > or = 14 on the BDI were seen by the psychiatrist for further assessment, and where appropriate, diagnoses were made according to DSM-III-R criteria. RESULTS: One hundred and ninety-two patients participated in the study; 95 scored > or = 14 on the BDI and one-third of these were found to have a depressive disorder. Factors significantly predictive of a BDI score > or = 14 were: an LEI score > 77; a diagnosis of acquired immunodeficiency syndrome (AIDS); being on sickness benefits or a pension; no current relationship; and a past history of depression. Few differences were demonstrated between those with a depressive disorder and those with a BDI score > or = 14 but no diagnosis of depressive disorder. Both groups had high mean PAIS scores indicating significant illness effects in multiple areas of function. CONCLUSIONS: Depressive symptoms are common among patients with HIV infection. Few factors differentiate between patients with a depressive disorder and those whose depressive symptoms do not meet diagnostic criteria. Substantial disability is present in both groups.

Fluoxetine treatment of depressed patients with HIV infection.

OBJECTIVE: The aim of this paper is to describe the outcome of fluoxetine treatment of depressed patients with HIV infection. METHOD: An open study was made of 20 patients with varying stages of HIV infection treated for depression with fluoxetine. RESULTS: 15 of 20 patients improved with fluoxetine treatment; the drug was generally well tolerated, with no significant drug-drug interactions. CONCLUSIONS: Fluoxetine appears to be effective for the treatment of depression in patients with HIV infection.

Isoniazid and antidepressants: is there cause for concern?

The antituberculous drug isoniazid has weak monoamine oxidase inhibiting properties. Drug and dietary restrictions generally applied to the use of monoamine oxidase inhibitors (MAOI) have not been routinely recommended with its use. Here we report three cases in which antidepressant drugs and isoniazid were co-administered. In two, adverse events, possibly due to an interaction between the drugs prescribed are described. We suggest that the combination of isoniazid and antidepressants be used with caution until further data are accumulated.