An integrated model of provision of palliative care to patients with cystic fibrosis.

Palliative care of patients with cystic fibrosis (CF) is often undertaken by CF teams rather than palliative care teams because of the specialist nature of the disease and the potential role of lung transplantation. We developed an integrated model of provision of palliative care whereby most care is delivered by the CF team using palliative guidelines and pathways, with additional support available from the specialist palliative care team when needed. We report our experience of the terminal care of 40 patients with CF with regard to the circumstances of death, lung transplantation status, specific symptoms and provision of palliative treatments. The transition from disease modifying treatments to palliative care was particularly complex. Patients had a high level of symptoms requiring palliation and most died in hospital. Palliative care is a crucial component of a CF service and requires the specialist skills of both the CF and palliative care teams.

Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review.

OBJECTIVE: To establish whether cannabis is an effective and safe treatment option in the management of pain. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches. STUDY SELECTION: Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score. DATA EXTRACTION: Independent data extraction; discrepancies resolved by consensus. DATA SYNTHESIS: 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common. CONCLUSION: Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.

Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.

OBJECTIVE: To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy. DESIGN: Systematic review. DATA SOURCES: Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000. STUDIES: 30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours. RESULTS: Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: "high" 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11. CONCLUSIONS: In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use.

A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.

We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.

Preparation and characterization of ZCAP blends.

Six different blends of zinc oxide, calcium oxide, phosphorous pentoxide (ZCAP) were prepared by mixing zinc oxide (ZnO), calcium oxide (CaO), and phosphorous pentoxide (P2O5) powders. The blends were 50:30:20, 48:32:20, 44:26:30, 40:40:20, 30:40:30, and 30:30:40, ZnO:CaO:P2O5 by weight, respectively. The mixed powders were calcined at 800 degrees C for 12 hours. Each blend was then characterized using X-ray diffraction. The X-ray diffraction patterns indicated that in some cases the reaction between oxides may not have gone to completion. Compositions of beta-3CaO.P2O5 and alpha-CaZn2(PO4)2 were found in many of the blends.

The population health impact of arthritis. POHEM Workshop Group.

The workshop was convened to develop quantitative estimates of the incidence of progressional musculoskeletal diseases in order to estimate the population health impact of arthritis. Estimates were developed for (a) the prevalence of arthritis, (b) a weighting strategy to adjust for the quality of life for the range of health states associated with arthritis, and (c) transition probabilities to represent the likelihood of disease onset and progression through the range of possible health states. A simulation "game" was designed to follow the progression of a cohort of 200 healthy persons or persons with arthritis, creating the basis for the estimation of transition probabilities and thus generating simulated longitudinal data that allow calculation of the quantitative estimate of the burden of illness from musculoskeletal diseases within the Canadian population.

Modelling the population health impact of musculoskeletal diseases: arthritis.

OBJECTIVE: A model adjusting for reductions in quality and quantity of life was developed to estimate the population health impact of musculoskeletal diseases. METHODS: Using arthritis as the prototype, prevalence, mortality, and severity data from a variety of sources were combined to model a hypothetical cohort of 1,000 individuals through life. Quality adjusted life years and population health expectancy were calculated for those with arthritis and compared to the general population. RESULTS: Without adjusting for quality of life, a cohort of 1,000 women and 1,000 men at age 15 years could expect 65,010 and 58,735 life years, respectively. Adjusting for quality of life, women with arthritis could expect 61,719 life years, and men 57,123 life years. The unadjusted population health expectancy was 65.0 for girls and 58.7 for boys (at age 15 years). Adjusting for quality of life, the population health expectancies were 61.7 and 57.1, years for women and men, respectively. CONCLUSION: Using this model, the typical adult woman with arthritis can expect to lose 3.3 healthy years of life, and a man, 1.6 healthy years of life. Overall, the model provided a general methodology for determining the population health impact of musculoskeletal diseases. In addition, it is hoped that the methodology will stimulate further research into this area, raise awareness about the uses and limitations of currently available data, and provide a useful model for monitoring the impact of interventions.

Hospital reimbursement in Alberta: outcomes management is on the way.

The Alberta government has initiated a process to alter fundamentally the way it pays hospitals. As with most provinces, Alberta has been paying hospitals for what they spend. The new Alberta model will initially pay hospitals for what they do and ultimately will pay hospitals for what they ought to do; that is, for the outcomes that should be achieved. This article describes the initial step of what is expected to be a lengthy journey. The principles underlying the model are: it should be a prospective case-based system; there should be performance linkages between types of hospitals; severity should be incorporated into the model; and cost or cost proxies should be used where possible in weight development and clinical concerns, both nursing and medical, should be addressed. For the past two years funding adjustments have been made on the basis of the calculation of a Hospital Performance Index (HPI). The HPI is the average predicted cost per case divided by the unweighted average actual cost per case. The HPI is intended as an interim measure only. Ultimately, the system will evolve into a true prospective case-based system with volume controlled via role statements and linked to clinical outcomes.

Electrical properties of ALCAP and ZCAP ceramics.

The electrical properties of implantable ceramics have been studied. The properties of resistivity, dielectric constant, magnetic permeability, and piezoelectric constant were measured using test methods developed to give reproducible results on common electrical instruments. The electrical properties of Aluminum Calcium Phosphorus Oxide (ALCAP) and Zinc Calcium Phosphorus Oxide (ZCAP) ceramics were measured with an ohmeter, impedance bridge, and oscilloscope in conjunction with special test fixtures. Both the ALCAP and ZCAP materials were characterized as insulating dielectrics with mean resistivities of 6.0E04 ohm.m and with mean dielectric constants of 5.3 for both ceramics. Neither the ALCAP nor the ZCAP exhibited magnetic or piezoelectric properties. The results indicate that these ceramics could be used as an insulative housing for a variety of medical devices.

Reactivity of catecholamines and related substances in the mouse lymphoma L5178Y cell assay for mutagens.

Using the L5178Y mouse lymphoma cell thymidine kinase locus and the Salmonella his locus assays, the mutagenic potentials of several catecholamines and related compounds were examined. No supplementary metabolic activation systems were used. In the mouse lymphoma assay, the dihydroxybenzenes catechol and hydroquinone had similar and appreciable mutagenic potentials, whereas resorcinol was less active. Derivatives of catechol, such as dopamine and epinephrine, were mutagenic, whereas the related monohydroxylated compounds tyramine and synephrine were inactive. The primary amine, arterenol, and the corresponding secondary amine, epinephrine, induced similar mutagenic responses. Carboxylation of the side chain of dopamine, giving L-dopa, reduced the maximum mutagenic response. The introduction of charged groups directly on to the aromatic ring also reduced mutagenic activity, while an intervening methylene reversed this effect. Thus, 3,4-dihydroxyhydrocinnamic acid was more active than 3,4-dihydroxybenzoic acid. The compound active at the lowest doses was 4-tert-butyl catechol. The activities of these compounds are highly dependent upon substituent groups. Experiments with superoxide dismutase gave circumstantial evidence for some of the mutagenic activity being due to superoxide anion. Active oxygen species might be responsible for some of the observed effects, but this cannot be concluded from the superoxide dismutase experiments. Mutagenic responses in Salmonella were very low but were significant for L-dopa in three strains and for epinephrine and arterenol in one strain. Limited DNA association studies of 14C-dopamine suggest interactions in L5178Y and Salmonella cells and in mouse liver. The mutagenicity of dopamine in L5178Y is reduced by high serum concentrations during the exposure period, while the apparent association with DNA is unaffected.

Direct endocardial recording from an accessory atrioventricular pathway: localization of the site of block, effect of antiarrhythmic drugs, and attempt at nonsurgical ablation.

We recorded a discrete 0.95 mV potential consistent with accessory atrioventricular pathway (AP) activation during serial electrophysiologic studies in a patient with Ebstein's anomaly and Wolff-Parkinson-White syndrome. Bipolar pacing from the catheter electrode in which the AP potential was recorded resulted in a stimulus-ventricle interval identical to the AP-ventricle interval during antegrade conduction, and a stimulus-atrium interval identical to the AP-atrium interval during retrograde conduction. With the patient in the drug-free state, antegrade AP block during atrial pacing and retrograde AP block during ventricular pacing occurred distal to the AP potential (AP-ventricle junction and AP-atrium junction, respectively), supporting the "impedance mismatch" hypothesis. Procainamide and disopyramide each lengthened the antegrade AP effective refractory period by affecting the AP-ventricle junction (possibly by decreasing the current generated by the AP). Both drugs also lengthened the retrograde AP effective refractory period but produced a greater effect on the ventricle-AP junction than on the AP-atrium junction, suggesting marginal geometry of the former. R wave synchronous shocks of 160 and 320 W-sec delivered between the catheter electrode recording the largest unipolar AP potential and a skin electrode produced transient, complete, antegrade block over the AP, suggesting the feasibility of this new nonsurgical technique for AP ablation.

Hypocholesterolemic action of dietary fiber unrelated to fecal bulking effect.

Twenty-two healthy volunteers took approximately 20 g/day of concentrated dietary fiber from either carrot, cabbage, apple, bran, or guar gum or 31 g from pectin, added for 3-week periods to controlled diets. Total serum cholesterol fell by 13% on both guar and pectin (P less than 0.01) with no significant change in high density lipoprotein cholesterol. Over the 3-week supplementation period, the other fibers were without effect with the exception of carrot, where both control and test high density lipoprotein levels fell (P less than 0.05 and less than 0.01, respectively). If, however, the 3rd week of the control was compared with the 3rd test week, the values for total cholesterol were 7% lower after apple (P less than 0.02) while after carrot the high density lipoprotein cholesterol level was 10% lower than the control (P less than 0.01). No significant change was seen in serum triglyceride or body weight either as judged by differences over the 3-week periods or by comparing test and control values at 3 weeks. Comparison of stool weights obtained in this study indicate that the fecal bulking action of dietary fiber is independent of its hypocholesterolaemic effect.

Hypomagnesaemic hypocalcaemia with hypokalaemia caused by treatment with high dose gentamicin.

A 12-year-old boy developed renal wasting of magnesium, calcium, and potassium, with secondary hypomagnesaemia, hypocalcaemia, and hypokalaaemia (without hyperaldosteronism) after treatment with 14 400 mg gentamicin over 4 months. Gentamicin should not be given for prolonged courses if less toxic antibiotics are suitable. If it used, plasma magnesium, calcium, and potassium levels should be monitored during and after treatment.

Cervical cytomegalovirus excretion in pregnant and nonpregnant women: suppression in early gestation.

Comparison of 659 pregnant and 202 nonpregnant women with similar demographic characteristics showed overall rates of cervical cytomegalovirus excretion that were identical (9.5% vs. 9.4%) and were surprisingly high, especially since 89% of the pregnant group possessed antibody to cytomegalovirus when admitted to the study. Prevalence of cytomegalovirus among gravidas was significantly lower during the first (1.6%) than during the third (11.3%) trimester. Thus, early pregnancy appeared to exert a suppressive effect on viral excretion that waned with advancing gestation. A similar but less significant occurrence was observed in the two groups with respect to viuria. Increasing age also appeared to suppress the virologic expression of cervical and urinary tract infection, whereas multiparity seemingly produced such an effect only in the cervix. Among both cervical and urinary excreters, a few shed virus thoughout pregnancy, and others shed virus intermittently; however, viral shedding most commonly began in late gestation and frequently continued into the postpartum period. Primary infection was not documented, and antibody status remained unchanged with the advent of viral excretion in most cases. Thus, reactivation of endogenous virus seems the most likely explanation for viral shedding in our population. Similar rates of isolation of Neisseria gonorrhoeae in excreters and nonexcreters further argue against the other major possibility, venereal reinfection.