Development of a decision analytic model to support decision making and risk communication about thrombolytic treatment.

BACKGROUND: Individualised prediction of outcomes can support clinical and shared decision making. This paper describes the building of such a model to predict outcomes with and without intravenous thrombolysis treatment following ischaemic stroke. METHODS: A decision analytic model (DAM) was constructed to establish the likely balance of benefits and risks of treating acute ischaemic stroke with thrombolysis. Probability of independence, (modified Rankin score mRS ≤ 2), dependence (mRS 3 to 5) and death at three months post-stroke was based on a calibrated version of the Stroke-Thrombolytic Predictive Instrument using data from routinely treated stroke patients in the Safe Implementation of Treatments in Stroke (SITS-UK) registry. Predictions in untreated patients were validated using data from the Virtual International Stroke Trials Archive (VISTA). The probability of symptomatic intracerebral haemorrhage in treated patients was incorporated using a scoring model from Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) data. RESULTS: The model predicts probabilities of haemorrhage, death, independence and dependence at 3-months, with and without thrombolysis, as a function of 13 patient characteristics. Calibration (and inclusion of additional predictors) of the Stroke-Thrombolytic Predictive Instrument (S-TPI) addressed issues of under and over prediction. Validation with VISTA data confirmed that assumptions about treatment effect were just. The C-statistics for independence and death in treated patients in the DAM were 0.793 and 0.771 respectively, and 0.776 for independence in untreated patients from VISTA. CONCLUSIONS: We have produced a DAM that provides an estimation of the likely benefits and risks of thrombolysis for individual patients, which has subsequently been embedded in a computerised decision aid to support better decision-making and informed consent.

A comparison of actual versus predicted emergency ambulance journey times using generic Geographic Information System software.

STUDY OBJECTIVE: The planning of regional emergency medical services is aided by accurate prediction of urgent ambulance journey times, but it is unclear whether it is appropriate to use Geographical Information System (GIS) products designed for general traffic. We examined the accuracy of a commercially available generic GIS package when predicting emergency ambulance journey times under different population and temporal conditions. METHODS: We undertook a retrospective cohort study of emergency ambulance admissions to three emergency departments (ED) serving differing population distributions in northeast England (urban/suburban/rural). The transport time from scene to ED for all the highest priority dispatches between 1 October 2009 and 30 September 2010 was compared with predictions made by generic GIS software. RESULTS: For 10,156 emergency ambulance journeys, the mean prediction discrepancy between actual and predicted journey times across all EDs was an underprediction of 1.6 min (SD 4.9). Underprediction was statistically significant at all population densities, but unlikely to be of clinical significance. Ambulances in urban areas were able to exceed general traffic speed, whereas, the opposite effect was seen in suburban and rural road networks. There were minor effects due to travel outside the busiest traffic times (mean overprediction 0.8 min) and during winter months (mean underprediction 0.4 min). CONCLUSIONS: It is reasonable to estimate emergency ambulance journey times using generic GIS software, but in order to avoid insufficient regional ambulance provision it would be necessary to make small adjustments because of the tendency towards systematic underprediction.

Modelling the efficiency of local versus central provision of intravenous thrombolysis after acute ischemic stroke.

BACKGROUND AND PURPOSE: Prehospital redirection of stroke patients to a regional center is used as a strategy to maximize the provision of intravenous thrombolysis. We developed a model to quantify the benefit of redirection away from local services that were already providing thrombolysis. METHODS: A microsimulation using hospital and ambulance data from consecutive emergency admissions to 10 local acute stroke units estimated the effect of redirection to 2 regional neuroscience centers. Modeled outcomes reflected additional journey time and accuracy of stroke identification in the prehospital phase, and the relative efficiency of patient selection and door-needle time for each local site compared with the nearest regional neuroscience center. RESULTS: Thrombolysis was received by 223/1884 emergency admissions. Based on observed site performance, 68 additional patients would have been treated after theoretical redirection of 1269 true positive cases and 363 stroke mimics to the neuroscience center. Over 5 years redirection of this cohort generated 12.6 quality-adjusted life years at a marginal cost of £6730 ($10,320, €8347). The average additional cost of a quality-adjusted life year gain was £534 ($819, €673). CONCLUSIONS: Under these specific circumstances, redirection would have improved outcomes from thrombolysis at little additional cost.

Fine Needle Aspiration Cytology for Neck Masses in Childhood. An Illustrative Approach.

The primary indication of fine-needle aspiration cytology of the head and neck region is a thyroid nodule or a mass located in the cervical area or the head. Although a thyroid nodule may raise the suspicion of malignancy, less than one in 20 cases results in a carcinoma. In addition, the list of differential diagnoses is quite different according to the age of the patient. A number of benign lesions, such as branchial cysts, sialadenosis, and sialoadenitis are often seen in childhood and youth. The malignant lesions that are on the top of the list of a pediatric mass of the head and neck (H&N) region include rhabdomyosarcoma, neuroblastoma, and papillary carcinoma of the thyroid gland. This critical review of the diagnostic features of a pediatric mass of the H&N region is accompanied by panels of several cytology features that may be of help to the cytopathologist and clinician.

Cognitive-behavioural therapy-based intervention to reduce fear of falling in older people: therapy development and randomised controlled trial - the Strategies for Increasing Independence, Confidence and Energy (STRIDE) study.

BACKGROUND: Falls cause fear, anxiety and loss of confidence, resulting in activity avoidance, social isolation and increasing frailty. The umbrella term for these problems is 'fear of falling', seen in up to 85% of older adults who fall. Evidence of effectiveness of physical and psychological interventions is limited, with no previous studies examining the role of an individually delivered cognitive-behavioural therapy (CBT) approach. OBJECTIVES: Primary objective To develop and then determine the effectiveness of a new CBT intervention (CBTi) delivered by health-care assistants (HCAs) plus usual care compared with usual care alone in reducing fear of falling. Secondary objectives To measure the impact of the intervention on falls, injuries, functional abilities, anxiety/depression, quality of life, social participation and loneliness; investigate the acceptability of the intervention for patients, family members and professionals and factors that promote or inhibit its implementation; and measure the costs and benefits of the intervention. DESIGN: Phase I CBTi development. Phase II Parallel-group patient randomised controlled trial (RCT) of the new CBTi plus usual care compared with usual care alone. SETTING: Multidisciplinary falls services. PARTICIPANTS: Consecutive community-dwelling older adults, both sexes, aged ≥ 60 years, with excessive or undue fear of falling per Falls Efficacy Scale-International (FES-I) score of > 23. INTERVENTIONS: Phase I Development of the CBTi. The CBTi was developed following patient interviews and taught to HCAs to maximise the potential for uptake and generalisability to a UK NHS setting. Phase II RCT. The CBTi was delivered by HCAs weekly for 8 weeks, with a 6-month booster session plus usual care. MAIN OUTCOME MEASURES: These were assessed at baseline, 8 weeks, 6 months and 12 months. Primary outcome measure Fear of falling measured by change in FES-I scores at 12 months. Secondary outcome measures These comprised falls, injuries, anxiety/depression [Hospital Anxiety and Depression Scale (HADS)], quality of life, social participation, loneliness and measures of physical function. There were process and health-economic evaluations alongside the trial. RESULTS: Four hundred and fifteen patients were recruited, with 210 patients randomised to CBTi group and 205 to the control group. There were significant reductions in mean FES-I [-4.02; 95% confidence interval (CI) -5.95 to -2.1], single-item numerical fear of falling scale (-1.42; 95% CI -1.87 to 1.07) and HADS (-1; 95% CI -1.6 to -0.3) scores at 12 months in the CBTi group compared with the usual care group. There were no differences in the other secondary outcome measures. Most patients found the CBTi acceptable. Factors affecting the delivery of the CBTi as part of routine practice were identified. There was no evidence that the intervention was cost-effective. CONCLUSIONS: Our new CBTi delivered by HCAs significantly improved fear of falling and depression scores in older adults who were attending falls services. There was no impact on other measures. FURTHER WORK: Further work should focus on a joint CBTi and physical training approach to fear of falling, more rational targeting of CBTi, the possibility of mixed group and individual CBTi, and the cost-effectiveness of provision of CBTi by non-specialists. TRIAL REGISTRATION: Current Controlled Trials ISRCTN78396615. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 56. See the NIHR Journals Library website for further project information.

CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP.

In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.

Medical disorders in people with recurrent depression.

BACKGROUND: Few studies have examined the rates of physical disorders in those with recurrent depression. AIMS: To examine self-reported physical disorders in people with recurrent depression compared with a psychiatrically healthy control group. METHOD: As part of a genetic case-control association study, 1546 participants with recurrent depression and 884 controls were interviewed about lifetime ever treatment for 16 different physical health disorders. RESULTS: The cases group had a significantly higher frequency of 14 physical disorders and more obesity than the control group. After controlling for age, gender, body mass index (BMI) and multiple testing, those in the cases group had significantly higher rates of gastric ulcer, rhinitis/hay fever, osteoarthritis, thyroid disease, hypertension and asthma. CONCLUSIONS: People with recurrent depression show high rates of many common physical disorders. Although this can be partly explained by BMI, shared aetiological pathways such as dysfunction of the hypothalamic-pituitary axis may have a role.

The rising share of nonmarital births: fertility choice or marriage behavior?

Much of the sharp rise in the share of nonmarital births in the United States has been attributed to changes in the fertility choices of unmarried and married women-in response, it is often argued, to public policy. In contrast, we develop and test a model that attributes the rise to changes in marriage behavior, with no necessary changes infertility. A variety of empirical tests strongly support this conclusion and invites focused attention to issues related to marriage behavior as well as to the interactions between marriage and fertility.