[Advanced directives in psychiatry: A review of the qualitative literature, a state-of-the-art and viewpoints]. / Les directives anticipées en psychiatrie : revue de la littérature qualitative, état des lieux et perspectives.

BACKGROUND: Advance Directives are written documents, which are used for people to notify their preference for a future situation when they are unable to give their consent. In psychiatry, psychiatric advance directives (PADs) can be used for patients with chronic psychotic disorders such as schizophrenia, or a bipolar disorder. PADs give the patient an opportunity to state wishes in advance about his/her treatment when he/she is in an acute state of illness. PADs were initially developed as a way for patients to defend themselves against the power of the psychiatrists, but are likely to become a useful tool in psychiatric care. PADs may contain information about medication, non pharmaceutical devices, and the name of a proxy decision maker. The main objective is to reduce the number of compulsory hospitalisations. OBJECTIVE: This article is a qualitative review which carries out a state-of-the-art on the use of PADs for people with chronic psychotic disorders and defines suggestions to include this intervention in the French psychiatric context. METHOD: We used the keywords psychiatric advance directives, crisis card, Ulysse directives, joint crisis plan (JCP) in the MEDLINE database to propose a qualitative review. We selected original clinical studies about the use of PADs for people with psychotic disorders. RESULTS: We included 36 articles. The qualitative analysis identified seven main themes: different types of PADs, effectiveness of PADs, practical use of PADs, patient's views, clinician's views, economical aspects, and legal aspects. The content of the PADs is consistent with psychiatric standard care in nearly all cases, regarding medical instructions, pre-emergency interventions, non-hospital alternatives and non-medical personal care. Patients use their PADs to describe prodromal symptoms of relapse and to suggest a treatment and a hospitalisation in advance. PADs are not used to refuse all treatments. Patients show a strong interest in creating a directive and a high level of satisfaction when using it. They feel they have more control over their mental health problem and are more respected and valued as a person. Thirty-six to fifty-three percent of clinicians had positive opinions regarding PADs. They valued the increase of the patient's autonomy and the prevention of relapse, but were concerned about difficulties for accessing the documents, and about the lack of training of the medical teams. Clinicians also feared the pressure of relatives or partners on treatment decisions. The qualitative analysis revealed the specific benefit of the JCP, a particular type of PADs negotiated with the medical team, on the reduction of the general number of admissions. We can identify practical problems such as the lack of accessibility to PADs in emergency situations, and the clinician's reluctance to use PADs. The only economical evaluation showed a non-significant decrease in total costs. DISCUSSION: PADs are used in a few countries, although their benefits in terms of patient's perceptions and compulsory admissions are promising. The JCP proposes a specific clinical approach based on therapeutic alliance. Its creation also involves the clinician, family members and a neutral mediator in a negotiated process. The JCP is likely to be the most efficient PAD model in reducing compulsory admissions. The use of the JCP appears to be relevant in the context of the new French legislation, establishing outpatient commitment orders and could be an effective way to improve the relationships with patients.

[Can concepts of neurodevelopment and neuroplasticity explain post-traumatic psychoses?]. / Les concepts de neurodéveloppement et neuroplasticité pourraient-ils expliquer les troubles psychotiques post-traumatiques ?

Cases of psychoses emerging after a brain injury, included in the diagnostic category "Pychotic disorder due to traumatic brain injury," are not rare in psychiatry. The authors suggest hypotheses aimed at furthering the understanding of the pathogenic mechanisms relating traumatic brain injuries to psychotic disorders. These hypotheses find their starting point in two concepts: neuronal plasticity and the neurodevelopmental theory of schizophrenia. Neuroplasticity is the ability of nerve cells to alter after internal or external changes. The neurodevelopmental theory of schizophrenia is based on the idea that early impairments in cerebral development could later lead to a schizophrenic disorder; this theory has been integrated into the concept of vulnerability to schizophrenia. The authors hypothesize that traumatic brain injuries lead to neuronal reshaping and that this reshaping could cause impairments in subjects vulnerable to schizophrenia.

[Prevalence of trauma-related disorders in the French WHO study: Santé mentale en population générale (SMPG)]. / Prévalence des troubles psychotraumatiques en France métropolitaine.

INTRODUCTION: Trauma-related disorders are disabling affections of which epidemiological data change according to the country, population and measuring instruments. The prevalence of posttraumatic stress disorder (PTSD) appears to have increased over the past 15 years, but one cannot tell whether it has indeed increased or whether the standardized procedure has improved. Moreover, very few epidemiologic studies among the general population have been conducted in Europe, notably in France. DESIGN OF THE STUDY: The "Santé mentale en population générale" (SMPG) survey, that took place in France between 1999 and 2003 among more than 36 000 individuals, gives an estimation of the prevalence of psychotraumatic disorders in the general population. Multi-varied analyses were performed on PTSD-related variables and comorbid disorders. The instantaneous prevalence (past month) of PTSD was of 0.7% among the whole SMPG sample, with almost the same proportion of men (45%) and women (55%). There was a high rate of comorbidity among PTSD individuals, notably with mood disorders, anxiety disorders and addictive behaviour. There was an obvious relationship with suicidal behaviour, with 15-fold more suicide attempts during the past month among the PTSD population. RESULTS: This survey analysed the consequences of a psychic traumatism over and above complete PTSD according to DSM-IV criteria, observing for instance the consequences for people exposed both to a trauma and suffering from at least one psychopathological symptom since the trauma. Those who suffered from a psychotraumatic syndrome, according to our enlarged definition, represented 5.3% of the population, half suffered from daily discomfort and a third of them used medication. Then, we compared those psychotraumatic syndromes to complete PTSD from a sociodemographic, functional and type of care point of view. There was little difference in prevalence of PTSD between men and women in the SMPG survey (45% vs 55%), which is clearly distinct from the other epidemiologic surveys named above. Regarding age, as in the ESEMeD survey, anxiety disorders appeared to be more frequent among younger people. The originality of the SMPG survey is obviously in the fact that it studied the functional impact of the psychic disorder, the type of care and the satisfaction level after care. Only 50% of the PTSD population feels sick which is, however, twice as high as for the psychotraumatized population. This doesn't fit either with the fact that 100% of the PTSD population say they feel uncomfortable with other people. The type of care is in the same vein: 50% of psychotherapies and 75% of medication, but also 25% of mild medicines and 25% of traditional medicines. Moreover, among the drugs, antidepressants (that are still the first choice treatment in all international recommendations) represent only 30%, whereas anxiolytics, hypnotics and phytotherapy represent the remaining 70%. DISCUSSION: Regarding the type of care, the differences between the psychotraumatized population and the PTSD population are obvious. They are obvious in that which concerns the type of care, since the medication is similar. From a very global point of view, patients suffering from a subsyndromal PTSD rarely choose medical care (religion, mild or traditional medicine), while full PTSD patients definitely choose classical medical care (drugs, psychotherapy, and 30% of hospitalization). The prevalence of those who ask for care is very close to that observed in the ESEMeD survey, which was four individuals out of 10 suffering from PTSD. CONCLUSION: The SMPG data show that its necessary to maintain the distinction between subsyndromal PTSD and full PTSD since the populations differ, but both need care.

Contemporary management of stage I testicular seminoma: a survey of Canadian radiation oncologists.

Recently published studies clearly indicate that there are now several acceptable options for managing stage i testicular seminoma patients after orchiectomy. We therefore decided to survey Canadian radiation oncologists to determine how they currently manage such patients and to compare the results with previous surveys. Our results demonstrate that adjuvant single-agent chemotherapy is being considered as an option by an increasing proportion of radiation oncologists (although it is not considered the preferred option), the routine use of radiotherapy is declining, and surveillance is becoming increasingly popular and is recommended most often.

The preferred treatment for stage I seminoma: a survey of Canadian radiation oncologists.

AIMS: To evaluate the preferences of radiation oncologists for managing stage I seminoma. MATERIALS AND METHODS: An electronic survey evaluating the management of stage I seminoma patients was sent to Canadian radiation oncologists to determine their treatment recommendations and preferences. RESULTS: The survey completion rate was 74% among eligible respondents (78/105). Most (56%) felt that surveillance was the preferred treatment for patients, whereas 31% thought that adjuvant radiotherapy was best, 1% chose adjuvant chemotherapy as being the preferred option and 12% were unsure. Most would choose the same treatment for themselves if they were diagnosed with stage I seminoma. A previously published survey found that most respondents considered radiotherapy as the best option. CONCLUSIONS: Most Canadian radiation oncologists now favour surveillance for most stage I seminoma patients.

A consensus development approach to define national research priorities in bone metastases: proceedings from NCIC CTG workshop.

AIMS: A 1-day workshop was conducted to gather interested Canadian radiation oncologists to identify priority research questions that could be answered through clinical trials under the auspices of the National Cancer Institute of Canada--Clinical Trials Group (NCIC-CTG) Symptom Control committee. MATERIALS AND METHODS: In preparation for the workshop, a survey of Canadian radiation oncologists resulted in four research areas in symptom control, including radiation-induced mucosal reactions, fatigue, radiotherapy for brain metastases and radiotherapy for bone metastases. The first half of the workshop consisted of plenary sessions where the research setting and perspective was defined for each area. This was followed by deliberations by a subgroup of researchers with special interest in the topic area. The bone-metastases subgroup deliberated the clinical context, the scientific merits and the required methodology of research questions related to the role of radiotherapy in early treatment of bone metastases, the role of re-irradiation, the role of systemic radiotherapy and patient selection for different fractionation schedules. A list of prioritised clinical studies was proposed. RESULTS: The question of single vs multi-fraction re-irradiation for symptomatic bone metastases was identified as most pertinent to the Canadian radiation oncologists present. A multi-centre, international intergroup study is undergoing protocol development. Other study concepts, such as an alternative dose-schedule of 17 Gy/2 fractions/1 week for intermediate-prognosis patients, and early referral for radiation oncologist assessment of early or mildly symptomatic bone metastases for good-prognosis patients, require further methodological development before a clinical trial can be proposed. CONCLUSION: An NCIC-CTG workshop provided an update on current evidence-based knowledge in palliative radiotherapy for bone metastases. New trial concepts were discussed among practitioners and clinical investigators to promote dialogue and collaboration. The proposal of an international intergroup randomised trial of single vs multiple fraction re-irradiation for painful bone metastases received the most support among participants.

Outpatient total body irradiation as a component of a comprehensive outpatient transplant program.

Outpatient total body irradiation (TBI) as part of a comprehensive outpatient transplant program was delivered to 142 of 167 (85%) consecutive patients receiving TBI-based conditioning therapy. Outpatients received either a single fraction of 500 cGy (110 patients) or 1200 cGy in six fractions over 3 days (32 patients). Patients were assessed daily and were administered oral ondansetron and dexamethasone for prophylaxis of nausea and vomiting as well as i.v. hydration. Accommodation during outpatient TBI-based conditioning was either the patient's home if within 30 min of the hospital, a hotel on the hospital grounds or on a closed hospital ward. None of the 142 patients required admission to the inpatient program during their TBI. There was no difference in 100-day mortality between those receiving TBI as an outpatient (9%) vs as an inpatient (16%). Of four deaths occurring within the first 14 days post transplant, none could be attributed to receiving TBI as an outpatient. Two hundred and six inpatient days were saved through the delivery of outpatient TBI. A comprehensive outpatient program, appropriate patient selection, daily hydration, the use of prophylactic 5HT3 antagonist anti-emetic therapy all contribute to the safe delivery of outpatient TBI.

Analysis of the properties of spores of Bacillus subtilis prepared at different temperatures.

AIMS: To determine the effect of sporulation temperature on Bacillus subtilis spore resistance and spore composition. METHODS AND RESULTS: Bacillus subtilis spores prepared at temperatures from 22 to 48 degrees C had identical amounts of dipicolinic acid and small, acid-soluble proteins but the core water content was lower in spores prepared at higher temperatures. As expected from this latter finding, spores prepared at higher temperatures were more resistant to wet heat than were spores prepared at lower temperatures. Spores prepared at higher temperatures were also more resistant to hydrogen peroxide, Betadine, formaldehyde, glutaraldehyde and a superoxidized water, Sterilox. However, spores prepared at high and low temperatures exhibited nearly identical resistance to u.v. radiation and dry heat. The cortex peptidoglycan in spores prepared at different temperatures showed very little difference in structure with only a small, albeit significant, increase in the percentage of muramic acid with a crosslink in spores prepared at higher temperatures. In contrast, there were readily detectable differences in the levels of coat proteins in spores prepared at different temperatures and the levels of at least one coat protein, CotA, fell significantly as the sporulation temperature increased. However, this latter change was not due to a reduction in cotA gene expression at higher temperatures. CONCLUSIONS: The temperature of sporulation affects a number of spore properties, including resistance to many different stress factors, and also results in significant alterations in the spore coat and cortex composition. SIGNIFICANCE AND IMPACT OF THE STUDY: The precise conditions for the formation of B. subtilis spores have a large effect on many spore properties.

Mechanisms of killing spores of Bacillus subtilis by acid, alkali and ethanol.

AIMS: To determine the mechanisms of killing of Bacillus subtilis spores by ethanol or strong acid or alkali. METHODS AND RESULTS: Killing of B. subtilis spores by ethanol or strong acid or alkali was not through DNA damage and the spore coats did not protect spores against these agents. Spores treated with ethanol or acid released their dipicolinic acid (DPA) in parallel with spore killing and the core wet density of ethanol- or acid-killed spores fell to a value close to that for untreated spores lacking DPA. The core regions of spores killed by these two agents were stained by nucleic acid stains that do not penetrate into the core of untreated spores and acid-killed spores appeared to have ruptured. Spores killed by these two agents also did not germinate in nutrient and non-nutrient germinants and were not recovered by lysozyme treatment. Spores killed by alkali did not lose their DPA, did not exhibit a decrease in their core wet density and their cores were not stained by nucleic acid stains. Alkali-killed spores released their DPA upon initiation of spore germination, but did not initiate metabolism and degraded their cortex very poorly. However, spores apparently killed by alkali were recovered by lysozyme treatment. CONCLUSIONS: The data suggest that spore killing by ethanol and strong acid involves the disruption of a spore permeability barrier, while spore killing by strong alkali is due to the inactivation of spore cortex lytic enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results provide further information on the mechanisms of spore killing by various chemicals.

Formaldehyde kills spores of Bacillus subtilis by DNA damage and small, acid-soluble spore proteins of the alpha/beta-type protect spores against this DNA damage.

Killing of wild-type spores of Bacillus subtilis with formaldehyde also caused significant mutagenesis; spores (termed alpha-beta-) lacking the two major alpha/beta-type small, acid-soluble spore proteins (SASP) were more sensitive to both formaldehyde killing and mutagenesis. A recA mutation sensitized both wild-type and alpha-beta- spores to formaldehyde treatment, which caused significant expression of a recA-lacZ fusion when the treated spores germinated. Formaldehyde also caused protein-DNA cross-linking in both wild-type and alpha-beta- spores. These results indicate that: (i) formaldehyde kills B. subtilis spores at least in part by DNA damage and (b) alpha/beta-type SASP protect against spore killing by formaldehyde, presumably by protecting spore DNA.

A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation.

The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) transplantation. Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation. Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant. Patients < or =70 kg received 300 microg/day and >70 kg 480 microg/day. All patients were reinfused with PBPCs with a CD34+ cell count >2.0 x 10(6)/kg. Baseline characteristics of age, sex and CD34+ cell count were similar between the two arms, the median CD34+ cell count being 5.87 x 10(6)/kg in the day +1 group and 7.70 x 10(6)/kg in the day +7 group (P=0.7). The median time to reach a neutrophil count of >0.5 x 10(9)/l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P=0.68). Similarly, there was no difference in median days to platelet recovery >20000 x 10(9)/l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P=0.83). There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P=0.7), intravenous antibiotic use (7 vs 8 days; P=0.54) or median number of red blood cell transfusions (4 vs 7 units; P=0.82) between the two arms. Median length of hospital stay was 11 days post-PBPC reinfusion in both groups. The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P < 0.0001). There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation. There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay. The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug costs. For patients with an adequately mobilized PBPC graft, the initiation of G-CSF can be delayed until day +7 post-PBPC reinfusion.

Continuous purification of porcine lipase by rotating annular size-exclusion chromatography.

Crude porcine lipase (triacylglycerol lipase, EC 3.1.1.3) was purified in a single-stage chromatographic process. The purification was accomplished in a batch, as well as in a continuous system. Two types of size-exclusion packing materials (Sephadex and Sephacryl) were used. The average x-fold increase in purity, and the average recovered activity in the batch Sephadex and Sephacryl experiments were 13.6 and 89.7%, and 34.2 and 98.8%, respectively. The average x-fold increase in purity and the average activity recovered in the continuous Sephadex and Sephacryl experiments were 27.1 and 82.5% and 16.2 and 89%, respectively. Flow visualization experiments were carried out by tagging the protein to be separated with a fluorescent dye. The results from these experiments are also reported in this article.

Interstitial brachytherapy for penile carcinoma: an alternative to amputation.

From 1987 to 1994, 15 patients with penile saquamous cell carcinoma were referred to the Ottawa Regional Cancer Centre. Seven had already been managed surgically. The other eight were treated with interstitial implantation. Mean age was 58 years (range 39-80). Two patients had previous incomplete local excision and six had biopsy only, with tumor from 1.5 to 4 cm in diameter. Six tumors were located on the glans, one on the corona and one at the base. All were clinically node negative. Six patients were implanted using a rigid technique with a fixed array of steel needles in pre-drilled plexiglass templates, and two with flexible nylon tubing. Implants were manually afterloaded with Iridium-192 wire. The prescribed dose of 60-65 Gy was delivered in 2.5-5.5 days. Local tumor control is 100% at a mean follow-up of 37 months (range 6-64). One patient died of metastases at 15 months with the primary controlled. The remaining seven patients are alive without evidence of disease. Six who were sexually active, continue to be so. One patient has a urethral stricture requiring dilatations. Cosmesis is generally good: mild to moderate hypopigmentation, telangiectasia and fibrosis may develop at the implant site. Intersititial brachytherapy for T1 or minimally invasive T2 penile squamous cell cercinoma up to 4 cm in diameter provides excellent local control with preservation of function and is a viable alternative to amputation.

A pilot study of intra-arterial carboplatin in patients with recurrent carcinoma of the cervix, postradiation.

Twelve patients with recurrent squamous cell carcinoma of the cervix restricted to the pelvis were treated with intra-arterial infusion of carboplatin. The initial carboplatin dose was 300 mg/m2, every 4 weeks, and the dose was escalated to 450 mg/m2. Myelosuppression was the dose-limiting toxicity at the 450 mg/m2 dose. One patient died of treatment-related febrile neutropenia at that dose level. Two patients having received one cycle at 300 mg/m2 suffered grade 3 peripheral paresthesia. There were no objective responses but five patients had a subjective improvement of pain and performance status.

A translating-bed technique for total-body irradiation.

Total-body irradiation (TBI) is a therapy modality that is being used with increasing frequency, in conjunction with chemotherapy, for patients undergoing bone-marrow transplantation. At the Ottawa Regional Cancer Centre a technique has been developed for the delivery of TBI to patients prior to bone-marrow transplantation. In this technique patients are treated on a mobile couch at approximately 195 cm SSD with a field size of 66.5 cm wide by 57 cm long. A computer-controlled stepping motor drives the patient couch at a user-selectable speed. The total dose delivered to the patient is a function of couch velocity, field size and patient separation. Treatment times are of the order of 10 min for each of the anterior and posterior fields for a 400 cGy fraction. It has been found that the conventional central axis tissue maximum ratio (TMR) and percentage depth dose (PDD) functions are not appropriate for describing dose delivered during dynamic treatment. To this end we have developed dynamic TMR and PDD functions. Extensive measurements have been performed in an anthropomorphic water phantom to determine the dose distributions in three dimensions and the efficacy of polymethyl methacrylate (PMMA) beam spoilers as a replacement for anterior and lateral bolus. It has been found that 2.4 cm PMMA spoilers do provide full skin dose and negate the requirement for lateral bolus. This TBI procedure is simple, rapid and appears to be well tolerated by the patients. 55 patients have been treated since the introduction of this technique in 1991.

Brachytherapy of neck metastases.

Brachytherapy with iridium 192 was used in 20 patients with recurrent or persistent neck metastases from a primary head and neck carcinoma. Nine patients had intra-operative brachytherapy in combination with a neck dissection. Three patients had an implant as a boost following external beam radiotherapy. Eight patients were treated by brachytherapy alone for unresectable neck recurrence ranging from 5 to 10 cm in diameter. Nineteen patients were evaluable for neck control: 15 patients had complete clearance of tumor and 13 patients were controlled at time of death or last follow-up. There were few complications from treatment. Five patients are alive at 5, 14, 16, 22, and 27 months post-implant with two patients having developed a second primary. Seven patients died from distant metastases, four from regional disease and four from intercurrent illness. Indications are summarized for this frequently forgotten but useful last option for patients with persistent or recurrent neck metastases.

Phase II study of lonidamine plus radiotherapy in the treatment of brain metastases.

Twenty-nine patients received the cytotoxic radiosensitizing agent lonidamine before, during, and after cranial irradiation for brain metastases. One patient was ineligible (meningioma). In 28 eligible patients, median survival was 29 weeks (range, 2 to > 220 weeks). Nine patients (32%) survived > 1 year and 3 (11%) survived > 2 years. The major toxic effects of lonidamine were myalgias, nausea and vomiting, somnolence, and ototoxicity. There was no evidence that radiation skin toxicity or cerebral toxicity was increased by the addition of lonidamine. None of the patients experienced shrinkage of their extracerebral disease on lonidamine. Median survival duration in this study was at the upper limit of that reported in the literature for radiation alone, and the proportion of 2 year survivors was also higher than usual for radiation alone. Hence, further studies may be warranted.