Risk of transition to schizophrenia following first admission with substance-induced psychotic disorder: a population-based longitudinal cohort study.

BACKGROUND: The potential for drugs of abuse to induce acute psychotic symptoms is well recognised. However, the likelihood of transition from initial substance-induced psychotic disorder (SIPD) to chronic psychosis is much less well understood. This study investigated the rate of SIPD transition to schizophrenia (F20), the time to conversion and other possible related factors. METHODS: Using data from the Scottish Morbidity Record, we examined all patients (n = 3486) since their first admission to psychiatric hospital with a diagnosis of SIPD [International Classification of Diseases, Tenth Revision (ICD-10) codes F10-F19, with third digit five] from January 1997 to July 2012. Patients were followed until first episode of schizophrenia (ICD-10 code F20, with any third digit) or July 2012. Any change in diagnosis was noted in the follow-up period, which ranged from 1 day to 15.5 years across the groups. RESULTS: The 15.5-year cumulative hazard rate was 17.3% (s.e. = 0.007) for a diagnosis of schizophrenia. Cannabis, stimulant, opiate and multiple drug-induced psychotic disorder were all associated with similar hazard rates. The mean time to transition to a diagnosis of schizophrenia was around 13 years, although over 50% did so within 2 years and over 80% of cases presented within 5 years of SIPD diagnosis. Risk factors included male gender, younger age and longer first admission. CONCLUSIONS: SIPD episodes requiring hospital admission for more than 2 weeks are more likely to be associated with later diagnosis of schizophrenia. Follow-up periods of more than 2 years are needed to detect the majority of those individuals who will ultimately develop schizophrenia.

Prevalence of anaemia before major joint arthroplasty and the potential impact of preoperative investigation and correction on perioperative blood transfusions.

BACKGROUND: Preoperative investigation and treatment of anaemia is recommended before orthopaedic surgery. We measured the prevalence of anaemia among admissions presenting for elective major joint arthroplasty (MJA), assessed their transfusion requirements, and investigated factors associated with perioperative blood transfusion. METHODS: All admissions to a dedicated elective orthopaedic hospital during 2000-2001 were studied. The patients' database was merged with the haematology and transfusion databases. Population estimates for different types of anaemia and their blood transfusion requirements were generated using local reference ranges (males <130 g litre(-1); females <115 g litre(-1)). RESULTS: One thousand three hundred and twenty-two admissions were included; haematology data were complete for 1142 (544 primary hip, 490 primary knee, 77 revision hip, 31 revision knee). About 19.6% were anaemic [7.1% haemoglobin (Hb) <110 g litre(-1); 1.6% Hb<100 g litre(-1)]. Overall, 21.3% of admissions were transfused (mean 0.58 units per case: 95% CI 0.50-0.61). For anaemic admissions, 42.0% were transfused (mean 1.11 units per case: 95% CI 0.90-1.32). Mean red cell use for admissions with normocytic normochromic anaemia (12.7% of admissions) and hypochromic anaemia (4.6%) was 1.04 (95% CI 0.78-1.31) and 1.14 (95% CI 0.71-1.57) units per admission, respectively. Factors strongly associated independently with transfusion were preoperative haemoglobin

Phase I clinical and pharmacologic study of weekly cisplatin combined with weekly irinotecan in patients with advanced solid tumors.

PURPOSE: In vitro synergy between cisplatin and irinotecan (CPT-11) has been reported. We designed a combination schedule of these agents to maximize the potential for synergistic interaction. PATIENTS AND METHODS: To maximize the opportunity for synergy, we divided the cisplatin into four consecutive weekly treatments, followed by a 2-week rest. Each dose of cisplatin was immediately followed by a dose of irinotecan. The dose of cisplatin was fixed at 30 mg/m2/wk. The initial irinotecan dose was 50 mg/m2/wk and this was escalated by 30% increments in successive cohorts of three to six patients to establish the maximum-tolerated dose (MTD). Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were analyzed. RESULTS: Of 35 patients with solid tumors enrolled onto this trial, 30 were assessable for toxicity and response. The MTD for this regimen was 30 mg/m2/wk of cisplatin plus 50 mg/m2/wk of irinotecan in previously treated patients and 30 mg/m2/wk of cisplatin plus 65 mg/m2/wk of irinotecan in chemotherapy-naive patients. Neutropenia was the dose-limiting toxicity (DLT) encountered in this trial. Diarrhea was infrequent and rarely dose-limiting. Seven of 30 assessable patients achieved a partial response. No alteration in irinotecan, SN-38, or SN-38G pharmacokinetics resulted from the administration of cisplatin with irinotecan. CONCLUSION: The administration of cisplatin and irinotecan on this weekly schedule provides a practical and well-tolerated regimen that has the potential to maximize any clinical synergy between the two agents. Evidence of substantial clinical activity was seen in this phase I study.

Initiation of self-grooming in resting rats by local PVH infusion of oxytocin but not alpha-MSH.

The present study was designed to discriminate between factors that initiate and/or prolong self-grooming. The study of factors initiating the grooming response is complicated by the fact that rats may groom already as a consequence of the injection procedure, due to release of endogenous substances after needle insertion or just handling of the animal. Therefore we used an infusion technique that allowed the rats to settle down quietly after they had been connected to an infusion pump, before the actual infusion of the peptide took place. In a previous report, we showed that direct injections of ACTH1-24 and alpha-melanocyte-stimulating hormone (alpha-MSH) into the paraventricular nucleus of the hypothalamus (PVH) prolong self-grooming caused by the injection procedure. Whether these peptides can also initiate grooming, however, is not yet clear. In this report, we compare the effects of alpha-MSH and oxytocin after infusion into the PVH in resting animals. Oxytocin is abundantly present in the PVH and is known to be involved in the regulation of grooming behavior. Slow infusions of oxytocin (0.1 microgram) do initiate grooming, but alpha-MSH (0.1 microgram) is without any behavioral effect. This suggests that oxytocin in the PVH is involved in the initiation of self-grooming, whereas alpha-MSH and probably ACTH do maintain grooming initiated otherwise, either by mechanical activation of the PVH and/or by the handling procedures. Infusion of substances in resting animals apparently is a way to avoid interactions between ongoing overt behavior and peptide-induced effects.

Nursing strategies for patients on oral chemotherapy.

Oncology nurses play a pivotal role in educating the cancer patient who is about to commence oral chemotherapy. Increasing numbers of patients are receiving oral chemotherapy at home, and with this move to oral self-administration, there has been a critical shift in responsibility of management from the provider to patient. Oral regimens pose new challenges in patient selection and education. Recognition of factors that affect patient compliance will be particularly important with oral chemotherapy. Strategy tools for the patient and provider will need to be developed to ensure optimal compliance and safety.

Postoperative radiation therapy for rectal cancer combined with UFT/leucovorin.

Postoperative combined-modality therapy with fluorouracil (5-FU) and radiation therapy is accepted practice for high-risk rectal cancer. Postoperative pelvic radiotherapy alone may improve pelvic control, but is not associated with an improvement in survival. Protracted infusional 5-FU has been associated with decreased tumor recurrence and improved survival when combined with postoperative adjuvant pelvic radiotherapy. The use of new drugs and alternative ways of administering 5-FU is desirable. UFT plus leucovorin is an oral 5-FU prodrug with efficacy equal to 5-FU plus leucovorin in metastatic colorectal cancer. A combination of postoperative adjuvant UFT plus leucovorin concurrent with radiation therapy should be feasible, and the design of an ongoing phase I trial is presented.

Zimelidine distribution in a sudden death.

The occurrence of zimelidine, a new experimental antidepressant, in a sudden death is presented. Tissues were extracted with n-butyl chloride. Quantitation was done by capillary gas chromatography with a nitrogen/phosphorus detector. Drug confirmation was obtained by gas chromatography and mass spectrometry. Blood concentrations of zimelidine and its metabolite norzimelidine were 0.71 and 2.2 mg/L respectively. Concentrations of the drug and metabolite are also given for the urine, liver, bile, and brain.

Monitoring quality of audit in obstetrics and gynaecology.

OBJECTIVE: To develop a questionnaire to assess audit activity and to use it to evaluate systematically the quality of audit in obstetrics and gynaecology within NHS hospitals in the UK. DESIGN: Retrospective review of 212 consecutive questionnaires completed at hospital recognition committee visits for training accreditation, between 1 January 1993 and 31 August 1998, validated against hospital trust annual audit reports. MAIN MEASURES: Use of seven quality criteria developed within the Royal College of Obstetricians and Gynaecologists clinical audit unit and also assessment of support for audit and participation in regional and national audit. Results were compared between 1993/4 (n = 72), 1995/6 (n = 72), and 1997/8 (n = 68) for evidence of improvement. RESULTS: After modifications to the questionnaire the version used from 1993 proved to be a satisfactory tool with minimal need for subsequent change. The results showed that there has been a significant improvement in the quality of obstetric and gynaecology audit with time (p < 0.0001) with 36 (53%) of departments in the previous two year period meeting all seven criteria. Similarly by this stage, 60 (88%) of departments had reached the stage of re-audit and 55 (81%) had conducted patient satisfaction surveys, both of these having significantly improved with time. Critical incident monitoring also became used more widely with time. Validation of topics audited was possible for 45% of hospitals where trust annual audit reports were available and these showed a high level of correlation. CONCLUSIONS: It has proved possible to conduct an audit of audit using the current system of hospital recognition visits for training accreditation. This has shown a great variety in the depth and breadth of audit that is being undertaken within individual obstetric and gynaecology departments. Since 1993 there has been an improvement in the quality of audit programmes undertaken, in particular in the number of hospitals carrying out critical incident monitoring, patient satisfaction surveys, and re-audit. This should be associated with improvements in staff training and in patient care.

From ministry to market. Catholic healthcare can survive in an age of commercialization.

Large, for-profit healthcare corporations now dominate hospital and physician services in many parts of the nation. Such organizations are under unrelenting pressure to produce profits; news stories show that these pressures can lead for-profits to engage in questionable, even illegal activities. Also, for-profits are unlikely to provide much care for the poor and uninsured. Unfortunately, Catholic providers have several disadvantages when competing with for-profits, and one is the fact that they do provide care for the poor. Catholic providers are handicapped also by: Problems with their geographic locations. Difficulties in creating partnerships with physicians. Lack of access to capital. Loss of political influence. On the other hand, Catholic healthcare providers have several advantages over for-profits. Among them are: A reservoir of public goodwill. Experience in forming networks The potential for prudent growth. A common vision. Access to Church pulpits. The influence of women and men religious Given theses advantages, Catholic health ministry leaders could boldly restructure their own organizations, and, in doing so, mitigate the commercialization of healthcare in the United States.

Effects of intravenous versus intragastric glucose pretreatment on triglyceride secretion by perfused livers of fed rats.

The effects of the route of administration of 450 mg [U-14C]glucose to 250-g fed rats in vivo on the subsequent release of triglycerides from the perfused liver was studied. Livers were perfused for 180 min using a nonrecycling medium containing 10 mM glucose, 2 mM lactate, 0.2 mM pyruvate, and 100 microunits/mL porcine insulin. Biopsies were obtained at the beginning and end of the perfusions. The perfusate was collected and the secreted triglycerides were analyzed. Slower absorption of the intragastric glucose load contrasted with the rapid entry of the intravenous load; however, the total liver counts were not significantly affected by the route of glucose delivery. Hepatic glycogen concentration was also not significantly different, but the percent of total liver counts which was present in glycogen was significantly higher after intravenous glucose. The majority of the radioactivity in the livers of both groups of rats was present in water-soluble metabolites, with lesser amounts in triglycerides and phospholipids. Radioactivity in hepatic triglycerides declined significantly during perfusion only in the rats which had received glucose intravenously. The mean rate of triglyceride secretion from the livers of rats receiving the glucose intravenously was significantly lower than that of the rats receiving glucose intragastrically (0.21 +/- 0.05 vs. 0.97 +/- 0.28 mg/g liver per 180 min, p less than 0.05). The route of glucose administration affects both entry of glucose into the blood and subsequent hepatic triglyceride metabolism and secretion.

Colposcopy and treatment of cervical intra-epithelial neoplasia: are national standards achievable?

OBJECTIVE: To assess whether consensus based national standards for colposcopy and treatment of cervical intra-epithelial neoplasia are achievable in practice. DESIGN: Identification of 100 consecutive cases of first assessment colposcopy from each gynaecological unit in the former North West region from 1 January 1994 and follow up of their outcome after one year. SETTING: All 19 gynaecological colposcopy clinics in the former North West region. SAMPLE: In one hospital data were available on only 39 women and therefore information was analysed on 1839 women. MAIN OUTCOME MEASURES: Waiting times for colposcopy, different modalities of treatment used for premalignant conditions of the cervix and type of anaesthesia used for treatments. With regard to follow up, time of occurrence, whether or not colposcopy was performed and efficacy of treatment as judged by cervical cytology. RESULTS: Waiting times for colposcopy varied in the individual hospitals studied, but overall 56% of patients were seen within eight weeks. Diathermy loop excision was the most popular treatment modality accounting for 44% of cases. At six months after treatment, 9.98% of patients had a smear of mild dyskaryosis or worse. Colposcopy, as well as cytology, was used at the first follow up visit in 43% of cases. CONCLUSION: At a local level individual hospitals can identify areas where improvements in the service they provide need to be made. The practicality of the current guidelines in today's health service needs questioning.

Arnold-chiari malformation in pregnancy.

We report the case of a 30-year-old pregnant woman with an Arnold-Chiari malformation, who presented with severe pregnancy-induced hypertension at 30 weeks gestation. She was known to have had a difficult tracheal intubation during a previous general anaesthetic. Caesarean section was performed under an incremental epidural anaesthetic block.

Comparison of i.v. and s.c. diamorphine infusions for the treatment of acute pain in children.

We have compared the i.v. and s.c. routes of administration for diamorphine infusions in children undergoing abdominal surgery. Subjects received general anaesthesia with extradural block and diamorphine up to 20 micrograms kg-1 h-1 after operation. There were no differences between the groups in diamorphine consumption, pain scores or incidence of side effects. The s.c. route appeared to be as effective and safe as the i.v. route for administration of diamorphine infusions in children undergoing elective surgery.

The optimal dose of ketamine for caudal epidural blockade in children.

Sixty boys aged up to 9 years undergoing orchidopexy were randomly allocated to receive one of three solutions for caudal epidural injection: group A received 1 ml.kg-1 of 0.25% bupivacaine with 0.25 mg.kg-1 of preservative-free ketamine, group B received 1 ml.kg-1 of 0.25% bupivacaine with ketamine 0.5 mg.kg-1 and group C received 1 ml.kg-1 of 0.25% bupivacaine with 1 mg.kg-1 of ketamine. Postoperative pain was assessed by means of a modified Objective Pain Score and analgesia was administered if this score exceeded four. The median duration of caudal analgesia was 7.9 h in group A, 11 h in group B and 16.5 h in group C. There were no differences between the groups in the incidence of motor block, urinary retention, postoperative vomiting or postoperative sedation. Group C had a significantly higher incidence of behavioural side effects, including slightly odd behaviour, vacant stares and abnormal effect than groups A and B.

Comparison of morphine sulphate and codeine phosphate in children undergoing adenotonsillectomy.

We undertook a double-blind study to evaluate equianalgesic doses of intramuscular morphine sulphate (0.15 mg.kg-1) and codeine phosphate (1.5 mg.kg-1) in 40 healthy children undergoing adenotonsillectomy. There were no significant differences in pain scores, analgesic requirements or sedation scores between the two groups over the following 24 h. More children vomited in the morphine group (60%) than the codeine group (30%) between one and six h after the procedure (P < 0.05). Codeine phosphate is associated with less postoperative vomiting than morphine sulphate while providing comparable postoperative analgesia for adenotonsillectomy.

Predictors of successful rehabilitation in long-stay patients.

Fifty-one long-stay psychiatric patients admitted to a new rehabilitation unit were followed up for 3-4 years. Two groups were identified, one (n = 29) where significant progress had been made, and a second (n = 22) where no significant progress had been made. The groups were compared on a number of demographic measures and on measures of mental state, social behaviour, self-care skills, and work performance in hospital. The only items which successfully differentiated the groups related to self-care skills such as use of money, catering ability, and care of clothes. The implications of these findings for future rehabilitation policy are discussed.

Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA ('ecstasy') users.

BACKGROUND: The use of MDMA ('ecstasy') is common among young people in Western countries. Animal models of MDMA toxicity suggest a loss of serotonergic neurons, and potentially implicate in the development of significant psychiatric morbidity in humans. AIMS: To test whether long-term use of MDMA can produce abnormalities in cerebral serotonin, but not dopamine, transporter binding measured by single photon emission computed tomography (SPECT). METHOD: Ten male regular ecstasy users and 10 well-matched controls recruited from the same community sources participated in SPECT with the serotonin transporter (SERT) ligand [123I] beta-CIT. Dopamine transporter binding was determined from scans acquired 23 hours after injection of the tracer. RESULTS: Ecstasy users showed a cortical reduction of SERT binding, particularly prominent in primary sensory-motor cortex, with normal dopamine transporter binding in lenticular nuclei. CONCLUSIONS: This cross-sectional association study provides suggestive evidence for specific, at least temporary, serotonergic neurotoxicity of MDMA in humans.