Development and validation of the Child Oral Health Impact Profile - Preschool version.

OBJECTIVE: The Child Oral Health Impact Profile (COHIP) is a validated instrument created to measure the oral health-related quality of life of school-aged children. The purpose of this study was to develop and validate a preschool version of the COHIP (COHIP-PS) for children aged 2-5. BASIC RESEARCH DESIGN: The COHIP-PS was developed and validated using a multi-stage process consisting of item selection, face validity testing, item impact testing, reliability and validity testing, and factor analysis. PARTICIPANTS: A cross-sectional convenience sample of caregivers having children 2-5 years old from four groups completed item clarity and impact forms. Groups were recruited from pediatric health clinics or preschools/daycare centers, speech clinics, dental clinics, or cleft/craniofacial centers. Participants had a variety of oral health-related conditions, including caries, congenital orofacial anomalies, and speech/language deficiencies such as articulation and language disorders. MAIN OUTCOME MEASURE: COHIP-PS. RESULTS: The COHIP-PS was found to have acceptable internal validity (a = 0.71) and high test-retest reliability (0.87), though internal validity was below the accepted threshold for the community sample. While discriminant validity results indicated significant differences across study groups, the overall magnitude of differences was modest. Results from confirmatory factor analyses support the use of a four-factor model consisting of 11 items across oral health, functional well-being, social-emotional well-being, and self-image domains. CONCLUSIONS: Quality of life is an integral factor in understanding and assessing children's well-being. The COHIP-PS is a validated oral health-related quality of life measure for preschool children with cleft or other oral conditions.

Real World Data in Adaptive Biomedical Innovation: A Framework for Generating Evidence Fit for Decision-Making.

Analyses of healthcare databases (claims, electronic health records [EHRs]) are useful supplements to clinical trials for generating evidence on the effectiveness, harm, use, and value of medical products in routine care. A constant stream of data from the routine operation of modern healthcare systems, which can be analyzed in rapid cycles, enables incremental evidence development to support accelerated and appropriate access to innovative medicines. Evidentiary needs by regulators, Health Technology Assessment, payers, clinicians, and patients after marketing authorization comprise (1) monitoring of medication performance in routine care, including the materialized effectiveness, harm, and value; (2) identifying new patient strata with added value or unacceptable harms; and (3) monitoring targeted utilization. Adaptive biomedical innovation (ABI) with rapid cycle database analytics is successfully enabled if evidence is meaningful, valid, expedited, and transparent. These principles will bring rigor and credibility to current efforts to increase research efficiency while upholding evidentiary standards required for effective decision-making in healthcare.

Fracture incidence and changes in quality of life in women with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO).

UNLABELLED: In this observational study of women with an inadequate clinical outcome to osteoporosis therapy, those with a fracture at baseline were more likely to sustain an incident fracture and have a worse health-related quality of life than those without prior fracture. INTRODUCTION: The Observational Study of Severe Osteoporosis (OSSO) was designed to assess the fracture incidence and health-related quality of life (HRQoL) in women with an inadequate clinical outcome to osteoporosis therapy. METHODS: Post-menopausal women (N=1,885) with established osteoporosis and an inadequate clinical response to osteoporosis drug therapy defined as: a) a fragility fracture despite therapy for one year (index fracture, N=988), or b) discontinued drug therapy due to adverse effects and/or non-compliance (N=897), were assessed during one year for HRQoL using the EQ-5D and the QUALEFFO questionnaires. RESULTS: One hundred and sixty-six (8.8%) women had a total of 209 incident fractures (1,139 fractures/10,000 women-years). Women with an index fracture were more likely to sustain an incident fracture than those without prior fractures (hazard ratio 1.91; 95% CI: 1.37-2.66; p<0.001). Co-morbidities or antidepressant use at baseline also increased the risk of incident fracture. Median total EQ-5D Health State Values and QUALEFFO scores were worse in women with an incident fracture regardless of index fracture status. The worst scores were reported in the EQ-5D sub-domains of self-care, usual activities and pain/discomfort. CONCLUSIONS: Women with an inadequate response to osteoporosis therapy had a high rate of incident fracture which had an adverse impact on HRQoL.

Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom.

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the findings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors influencing cost effectiveness were identified and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine significantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by 799 UK pounds (95% CI: - 1,824 UK pounds, 59 UK pounds) driven by reduced inpatient days--but the cost difference was not statistically significant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would significantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium.

Characterization of patients with an inadequate clinical outcome from osteoporosis therapy: the Observational Study of Severe Osteoporosis (OSSO).

BACKGROUND: Osteoporotic fractures remain a major public health problem. Currently available osteoporosis therapies significantly reduce the risk of fractures, but up to 50% of patients have an inadequate clinical outcome to therapy. AIM: To describe the clinical and quality of life (QOL) of a study population meeting a proposed definition of inadequate clinical outcome to osteoporosis therapy, recruited for the Observational Study of Severe Osteoporosis (OSSO). DESIGN: Cross-sectional, observational study. METHODS: Post-menopausal women with osteoporosis (n = 2314) were divided into Group 1 (those who had previously experienced a fragility fracture despite osteoporosis drug therapy for at least 12 months) (n = 1309, 57%), or Group 2 (those who had previously discontinued osteoporosis drug therapy due to non-compliance or side-effects) (n = 1005; 43%). Baseline clinical characteristics, quality of life (QOL) and osteoporosis/falls risk factors were analysed. RESULTS: The overall population had low BMD (mean +/- SD T-score at lumbar spine -3.1 +/- 1.1), and risk factors for fracture such as previous fractures (67.8%), family history (15.1%), and prolonged glucocorticoid use (17.5%). QOL was poor: total QUALEFFO and EQ-5D scores were 46.8 +/- 18.7, and 0.50 +/- 0.33, respectively. Patients in Group 1 had higher age and body mass index, fewer hours of exercise, more previous fragility fractures and falls, and poorer QOL scores. DISCUSSION: Our definition of inadequate clinical outcome from osteoporosis drug therapy identifies a severe osteoporosis cohort with poor QOL and increased fracture risk. Using such a definition may lead to earlier recognition of inadequate clinical outcome to osteoporosis therapy, and improved interventions and results.

Cost effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in the United Kingdom.

Drotrecogin alfa (activated) is licensed in Europe for the treatment of severe sepsis in patients with multiple organ failure. We constructed a model to assess the cost effectiveness of drotrecogin alfa (activated) from the perspective of the UK National Health Service when used in adult intensive care units. Patient outcomes from a 28-day international clinical trial (PROWESS) and a subsequent follow-up study (EVBI) were supplemented with UK data. Cost effectiveness was assessed as incremental cost per life year and per quality adjusted life year saved compared to placebo alongside best usual care. Applying the 28-day mortality outcomes of the PROWESS study, the model produced a cost per life year saved of 4608 UK pounds and cost per quality adjusted life year saved of 6679 UK pounds. Equivalent results using actual hospital outcomes were 7625 UK pounds per life year and 11,051 UK pounds per quality adjusted life year. Drotrecogin alfa (activated) appears cost effective in treating severe sepsis in UK intensive care units.

Effect of vascular occlusion on radiofrequency ablation of the liver: results in a porcine model.

OBJECTIVE: This study determined the effect of vascular occlusion on radiofrequency lesion shape, volume, and temperature in a porcine liver model. SUBJECTS AND METHODS: Radiofrequency lesions (n = 33) were created in the livers of six domestic pigs in vivo using a multiprong radiofrequency electrode. Lesions were randomly assigned to one of four vascular occlusion groups: portal vein, hepatic artery, Pringle maneuver (both hepatic artery and portal vein), or no occlusion. Radiofrequency parameters were time, 7 min; power, 50 W; and target temperature, 100 degrees C. Temperatures were measured 5, 10, and 15 mm from the electrode. After the animals were sacrificed, the lesions were excised. Lesion volume, diameter, and shape; maximum temperature; and time exposed to lethal temperatures (42-60 degrees C) were determined. RESULTS: Lesion volume was greatest with the Pringle maneuver lesions (12.6 +/- 4.8 cm(3)), followed by occlusion of the portal vein (8.6 +/- 3.8 cm(3)), occlusion of the hepatic artery (7.6 +/- 2.9 cm(3)), and no occlusion (4.3 +/- 1.0 cm(3)) (p < 0.05). Maximum lesion diameter was similar with the Pringle maneuver (3.3 +/- 0.3 cm), the portal vein (3.3 +/- 0.2 cm), and the hepatic artery (3.2 +/- 0.2 cm) groups compared with no occlusion (2.6 +/- 1.0 cm) (p < 0.05). Minimum lesion diameter ranged from 2.9 cm for Pringle maneuver lesions to 1.0 cm for lesions with no occlusion (p < 0.05). Vascular occlusion increased the time tissue was exposed to lethal temperatures (> 42-60 degrees C) and created more spherical lesions than no occlusion. CONCLUSION: Vascular occlusion combined with radiofrequency ablation increases the volume of necrosis, creates a more spherical lesion, and increases the time tissue is exposed to lethal temperatures when compared with radiofrequency alone. Most of this vascular occlusion effect could be accomplished with hepatic artery occlusion alone.

Acute hepatitis after ingestion of herbs.

Herbal preparations are marketed as natural and safe alternatives to conventional medicines for the prevention and treatment of a variety of ailments. However, consumers may not be fully aware of their potential side effects. We report two cases of acute hepatitis after the ingestion of herbal preparations. One of the mixtures included chaparral and bee pollen; the other was pure bee pollen. Chaparral has been reported to have similar effects in other patients, but we found no reports of acute hepatitis from bee pollen. We discuss chaparral and several other hepatotoxic herbs and review the literature. Our case reports remind primary care physicians to ask their patients about herbal use and discuss their potential toxicities.

Fentanyl produces cholinergically-mediated analeptic and EEG arousal effects in rats.

Fentanyl (20 micrograms/kg i.p.), administered to naltrexone-pretreated, pentobarbital-anesthetized rats, produced a shortening of the duration of narcosis. This analeptic effect was blocked by atropine, but not by methylatropine, indicating that a central cholinergic mechanism was involved. Fentanyl also increased sodium-dependent high affinity uptake of choline activity in the hippocampus and cortex that had been depressed by the barbiturate. Injection of 0.8 ng of fentanyl into the pontis oralis in the pontine reticular formation also produced analepsis in naltrexone-pretreated, pentobarbitalized rats. Hippocampal EEG recordings also showed the appearance of cholinergically-mediated theta activity, which was indicative of arousal activity in the hippocampus. These results suggest that fentanyl, in addition to possessing potent opiate activity, also activates a nonopioid-mediated central cholinergic arousal system.

Codeine produces a cholinergically mediated analeptic effect in rats and rabbits.

The intravenous administration of codeine to diazepam-narcotized rabbits resulted in a shortened duration of loss of righting reflex. Coadministration of naltrexone plus codeine enhanced this analeptic effect and was also effective in shortening the duration of pentobarbital narcosis. The analeptic effect was blocked by atropine, but not by methylatropine, indicating involvement of a central cholinergic mechanism. In rats the analeptic activity correlated with the reversal of the diazepam-induced fall in sodium dependent high affinity choline uptake in hippocampal and cortical synaptosomes. These findings may represent the pharmacological basis of the recently reported antinarcoleptic action of codeine in man.

Termination of ouabain-induced cardiac arrhythmias by anterior hypothalamic stimulation.

Digitalis-toxic ventricular arrhythmias were produced in cats by repeated injections of ouabain. These arrhythmias converted to normal sinus rhythm significantly faster in cats receiving anterior hypothalamic stimulation than in sham stimulated controls. This effect was uncorrelated with changes in sympathetic activity along the renal nerve.

Dual actions of lysergic acid diethylamide tartrate (LSD), 2-bromo-D-lysergic acid diethylamide bitartrate (BOL) and methysergide on dorsal root potentials evoked by stimulation of raphe nuclei.

A variety of drugs reported to antagonize serotonin were found to affect spinal cord potentials evoked by electrical stimulation of the caudal raphe nuclei of the cat. These brain stem-evoked dorsal root potentials (DRPs) consisted of a short latency depolarization (DRP-1), which was evoked by stimulation of a wide variety of sites in the medial brain stem and a long latency potential (DRP-2), which was elicited only when stimuli were applied near the raphe. The ability of serotonergic antagonists to increase or decrease these DRPs was dependent on the dose of the drug administered. High doses of lysergic acid diethylamide tartrate (LSD), 2-bromo-D-lysergic acid diethylamide bitartrate (BOL), methysergide and cinanserin each produced an immediate inhibition of DRP-2 and a simultaneous enhancement of DRP-1, both of which recovered by approximately 30 min. Each of the drugs produced a dose-related inhibition of DRP-2 at high doses, with LSD being the most potent and cinanserin the least potent. In contrast, low doses of LSD, BOL and methysergide elicited little or no immediate change in either DRP-2 or DRP-1, but produced an enhancement of DRP-2 which developed slowly over a period of 60 to 90 min. This increase in DRP-2 was most dramatic after administration of LSD and was not accompanied by changes in DRP-1. The inhibition of DRP-2 by high doses of LSD, BOL, methysergide and cinanserin may result primarily from inhibition of postsynaptic serotonergic receptors located on the primary afferent terminals. The increase in DRP-2 produced by low doses of LSD, BOL and methysergide is postulated to result from an interaction with receptors distinct from those which produced the inhibition of DRP-2 at higher doses.

Selective activation of nicotinic and muscarinic transmission in cardiac sympathetic ganglion of the dog.

The myocardial contractile responses to electrical stimulation of different segments of the thoracic sympathetic trunk in the pentobarbital-anesthetized dog were studied. Electrical stimulation of the sympathetic trunk between the second and third thoracic ramus and caudal limb of the ansa subclavia elicited myocardial contractile responses which were not completely antagonized by the ganglionic blocking agent chlorisondamine. Atropine in addition to chlone had no effect. When the sympathetic trunk between the third and fourth ramus was electrically stimulated, the response was partially antagonized by atropine as well as by chlorisondamine alone. From these results, it is suggested that impulses travelling via the third thoracic ramus or above it mediate myocardial contractile responses in which the nicotinic type response predominates whereaas impulses travelling via the fourth thoracic ramus or below it mediate myocardial contractile responses in which the muscarinic type predominates. additionally, evidence presented indicates that a major proportion of both nicotinic and muscarinic receptors mediating myocardial contractile changes are located in the caudal cervical ganglion rather than the stellate ganglion of the dog.