Stick or twist? Cost-effectiveness of siponimod compared with continuing existing disease-modifying therapies in the treatment of active secondary progressive multiple sclerosis in the UK.

OBJECTIVE: Identification of the phenotypic transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive multiple sclerosis (SPMS) is often delayed due to disease complexity and an unwillingness to withdraw RRMS disease-modifying therapies (DMTs), driven by limited SPMS treatment options. Despite the paucity of clinical evidence for efficacy in patients with SPMS, DMTs licensed for RRMS are frequently continued into the early stages of SPMS. The cost-effectiveness of oral siponimod, an active SPMS DMT, versus continued oral or infused RRMS DMTs for patients with active SPMS, was evaluated. METHODS: A cohort Markov model based on disease progression through Expanded Disability Status Scale health states, with annual cycles and lifetime horizon, was employed to determine the cost-effectiveness of siponimod from a UK National Health Service (NHS) perspective for patients with active SPMS. Baseline characteristics, health state utility values, hazard ratios for time to 6-month confirmed disability progression, annualized relapse rate ratios and adverse events for siponimod were obtained from the phase 3 EXPAND clinical trial, supplemented by published literature. Published costs, resource use data and comparator efficacy data were obtained from the literature and, in the absence of data, reasonable assumptions were made. RESULTS: Quality-adjusted life years (QALYs) were greater for siponimod versus all comparators (3.45 versus 2.69-2.83). Incremental cost-effectiveness ratios (ICERs), calculated as cost per QALY, for siponimod versus natalizumab (dominant), ocrelizumab (£4,760), fingolimod (£10,033) and dimethyl fumarate (£15,837) indicated that siponimod was cost-effective at the commonly accepted willingness-to-pay threshold of £30,000/QALY. CONCLUSIONS: Recognition of active SPMS and treatment of this phenotype with siponimod offers a cost-effective and clinically beneficial treatment approach compared with the continuation of oral or infused RRMS DMTs.

Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Örebro, Sweden, 1963-2010.

BACKGROUND: Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown. AIM: To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010. METHODS: Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Örebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005. RESULTS: The annual age-standardised incidence increased from 3.5 to 18.5 per 100 000 during the study period (P < .01). Correspondingly, the prevalence increased from 44 to 474 per 100 000 between 1965 and 2010. A higher proportion of males than females had extensive colitis at diagnosis (odds ratio: 1.55; 95% CI 1.17-2.05; P < .01). The risk for progression in disease extent was 34.5% and 18.5% at 10 years, for patients with proctitis and left-sided colitis, respectively (P < .01). The use of 5-aminosalicylates, within 10 years, rise from 79% to 92% between 1963-1975 and 1976-1990 (P < .01). Thiopurine use increased from 7% in 1976-1990 to 34% during 1991-2005 (P < .01). The colectomy rate at 10 years was 13.5% (95% CI 11.1%-15.8%), and the risk was lower among patients diagnosed in 1991-2005 compared to 1963-1975 (adjusted hazard ratio: 0.61; 95% CI 0.39-0.94; P = .02). CONCLUSION: The incidence and prevalence of UC increased over time, and the observed prevalence in 2010 is among the highest reported. In parallel, a decrease in colectomy rates was observed during the most recent decades, potentially reflecting improved medical treatment.

Remarriage after divorce and depression risk.

As marriage is associated with lower depression rates compared with being single in men, we aimed to examine if remarriage compared with remaining divorced is also associated with a reduced depression risk. Swedish register data were used to define a cohort of men who were born between 1952 and 1956 and underwent a compulsory military conscription assessment in adolescence. This study population comprised men who were divorced in 1985 (n = 72,246). The risk of pharmaceutically treated depression from 2005 to 2009 was compared for those who remarried or remained divorced between 1986 and 2004. Cox proportional hazards analysis was used to estimate hazard ratios for the risk of depression identified by pharmaceutical treatment, with adjustment for a range of potential confounding factors including childhood and adulthood socioeconomic circumstances, cognitive, physical, psychological and medical characteristics at the conscription assessment. The results showed that, even though divorced men who remarried had markers of lower depression risk in earlier life such as higher cognitive and physical function, higher stress resilience and socioeconomic advantages than men who remained divorced, remarriage was associated with a statistically significant elevated risk of depression with an adjusted hazard ratio (and 95% confidence interval) of 1.27(1.03 1.55), compared with men who remained divorced. Remarriage following divorce is not associated with a reduced risk of depression identified by pharmaceutical treatment, compared with remaining divorced. Interpersonal or financial difficulties resulting from remarriage may outweigh the benefits of marriage in terms of depression risk.

Analysis of health-related quality of life and costs based on a randomised clinical trial of escitalopram for relapse prevention in patients with generalised social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is associated with substantial reduction in health-related quality of life (HRQoL). Escitalopram has proven efficacy in the short-term treatment of SAD and prevention of relapse. OBJECTIVES: To determine whether the clinical effects of treatment translated into HRQoL benefits and to investigate costs of SAD treatment. METHODS: Data on HRQoL and resource utilisation were collected in a previously published clinical trial of escitalopram in relapse prevention. Among 517 patients, 371 responded to 12 weeks of open-label treatment with escitalopram and were randomised to escitalopram or placebo for 24 weeks. HRQoL was assessed using the short form (SF)-36 instrument and SF-6D utilities (preference-based index scores for overall HRQoL) were calculated. Costs were calculated for responders over the acute phase and for non-relapsed patients over the continuation phase, applying UK unit costs. RESULTS: Health-related quality of life was significantly improved after the acute phase when compared with baseline. The SF-6D utility increased by 0.047 in responders (p < 0.0001) and 0.021 in non-responders (p = 0.0005). Healthcare costs were non-significantly lower in acute phase than during prestudy phase (p = 0.0587 from NHS perspective), as were productivity costs (p = 0.1440). HRQoL at last visit was lower in relapsed than non-relapsed patients. The difference in utility was -0.026 (p = 0.0007). Healthcare and productivity costs were non-significantly lower in the escitalopram group than in the placebo group. CONCLUSIONS: Both effective acute treatment of SAD and prevention of relapse with escitalopram are associated with significant HRQoL benefits. Despite some limitations, the cost analysis suggests that savings in physician-visits and inpatient care may offset drug acquisition costs.

Domestic labour, paid employment and women's health: analysis of life course data.

The relationship between the amount of domestic labour performed by a woman during her lifetime and a variety of self-reported and objective measures of her health in early old age was examined in the female members (n = 155) of a data set containing considerable life course information, including full household, residential and occupational histories. Domestic labour, on its own, proved a weak predictor of health. The relationship strengthened when domestic labour was combined with the hazards of the formal paid employment which the woman had performed. This suggests that it is the combination of domestic labour plus paid employment which influences women's health. The robustness of this conclusion is indicated by its agreement with other studies which reached the same conclusion through an analysis of data with markedly different characteristics.

An assessment of selective serotonin reuptake inhibitor discontinuation symptoms with citalopram.

The selective serotonin reuptake inhibitors (SSRIs) have recently been associated with a variety of somatic and psychiatric symptoms upon abrupt drug discontinuation. These symptoms have been variously termed SSRI withdrawal, or SSRI discontinuation syndrome. Although all of the available SSRIs have been reported to cause discontinuation symptoms, some appear to have a greater propensity to cause these adverse events than others. Data from a previously completed placebo-controlled, double-blind study designed to assess citalopram in depression relapse prevention were analysed to assess patients for the emergence of discontinuation effects following randomization to placebo after 8 weeks of active drug treatment. Side-effects that occurred during the first 2 weeks following randomization to active drug (n = 150) or placebo (n = 72) were measured using the UKU unwanted side-effect list. The proportion of patients that experienced one or more events over the 2-week period following randomization was similar in the two groups, and there was no association between citalopram dose prior to randomization and the reporting of symptoms. Most of the events that did occur were mild in intensity and none resulted in discontinuation from the study. Events occurring at a higher frequency in the placebo group were most associated with the central nervous system (CNS). These events may reflect a re-emergence of depressive symptoms, since only 14.8% of patients randomized to placebo who did not relapse experienced CNS events, a low symptom incidence that was non-significant (P = 0.562) compared to patients continuing treatment (10.9%). Therefore, this assessment suggests that any symptoms associated with rapid discontinuation of citalopram are mild and transient, and emphasizes the significant role re-emerging depression and / or anxiety may play in the assessment and identification of SSRI discontinuation symptoms.

Social functioning in depression: a review.

OBJECTIVE: This article reviews the available data on social functioning in depression and provides clinical guidelines and opinion on this important and expanding field. DATA SOURCES: A MEDLINE search was conducted to identify all English-language articles (1988-1999) using the search terms depression and social functioning, depression and social adjustment, depression and psychosocial functioning, and social functioning and antidepressant. Further articles were obtained from the bibliographies of relevant articles. DATA SYNTHESIS: Depressive disorders are frequently associated with significant and pervasive impairments in social functioning, often substantially worse than those experienced by patients with other chronic medical conditions. The enormous personal, social, and economic impact of depression, due in no small part to the associated impairments in social functioning, is often underappreciated. Both pharmacologic and psychotherapeutic approaches can improve social impairments, although there is a lack of extended, randomized controlled trials in this area using consistent assessment criteria. CONCLUSION: Despite this lack, it is becoming clear that not all treatments are equally effective in relieving the impaired social functioning associated with depressive disorders. Furthermore, efficacy in relieving the core symptoms of depression does not necessarily guarantee efficacy in relieving impaired social functioning.

Service utilization among homeless and runaway youth in Los Angeles, California: rates and reasons.

PURPOSE: To describe the service utilization patterns of homeless and runaway youth in a "service-rich" area of Los Angeles, California; identify demographic and other correlates of utilization; and contextualize the findings with qualitative data. METHOD: During Phase 1 of this study, survey data were collected from an ethnically diverse sample of 296 youth aged 13-23 years, recruited from both service and natural "hang-out" sites using systematic sampling methods. During Phase 2, qualitative data were collected from 46 youth of varying ethnicities and lengths of time homeless. RESULTS: Drop-in centers and shelters were the most commonly used services (reported by 78% and 40%, respectively). Other services were used less frequently [e.g., medical services (28%), substance abuse treatment (10%) and mental health services (9%)]. Utilization rates differed by ethnicity, length of time in Los Angeles, and city of first homeless episode (Los Angeles versus all others). Shelter use was strongly associated with use of all other services. Despite youths' generally positive reactions to services, barriers were described including rules perceived to be restrictive, and concerns youth had about confidentiality and mandated reporting. Youth suggested improvements including more targeted services, more long-term services, revised age restrictions, and more and/or better job training and transitional services to get them off the streets. CONCLUSIONS: Because shelters and drop-in centers act as gateways to other services and offer intervention potential for these hard-to-reach youth, it is vital that we understand the perceived barriers to service utilization.

The persisting effect of unemployment on health and social well-being in men early in working life.

In our studies of the effects of unemployment in the early working life of men in a British national birth cohort we have shown elsewhere that this experience was part of a longer term accumulation of social and health disadvantage. This present study asks whether men's unemployment also inflicted potential longterm damage to future socio-economic chances and health. We therefore constructed indicators of socio-economic circumstances and health at 33 years from factors already shown to be associated with health in later life. For the socio-economic indicator we used a combination of income, occupational status and home ownership and described this as socio-economic capital. For the health indicator we combined scores of body mass index, leisure time exercise, frequency of eating fresh fruit and of smoking, and described this as health capital. After controlling for pre-labour market socio-economic and health factors, prolonged unemployment is shown here to reduce significantly both socio-economic and health capital by age 33 years. We conclude that the experience of prolonged unemployment early in the working life of this population of young men looks likely to have a persisting effect on their future health and socio-economic circumstances.

Side effects, dropouts from treatment and cost consequences.

Estimating the cost of treatment of depression has to take into account the quantifiable direct costs of medication, and hospital and community care, and the indirect costs such as loss of productivity, unemployment, costs of social support, etc. It also has to take into account the intangible costs to the depressed individual which are more difficult to quantify. Depression is a long-term illness and is associated with considerable morbidity and mortality which contribute substantially to the indirect costs of the illness. Successful treatment can be expected to reduce the overall costs of depression to the individual and to society at large. Compliance with treatment is an essential factor in the successful treatment of depression. Meta-analyses of published papers have indicated that significantly more patients discontinue treatment with tricyclic antidepressants due to side effects than with selective serotonin reuptake inhibitors and therefore better tolerated antidepressants should be the first choice of treatment. Pharmacoeconomic studies that take account of the failure of treatment represented by the discontinuations due to side effects show that an apparently cheaper antidepressant like imipramine may turn out to be more expensive than the better tolerated antidepressants.

Health and the life course: why safety nets matter.

This article argues that a life course approach is necessary to understand social variations in health. This is needed in order to take into account the complex ways in which biological risk interacts with economic, social, and psychological factors in the development of chronic disease. Such an approach reveals biological and social "critical periods" during which social policies that will defend individuals against an accumulation of risk are particularly important. In many ways, the authors of modern welfare states were implicitly addressing these issues, and the contribution of these policies to present day high standards of health in developed countries should not be ignored.

Health and social precursors of unemployment in young men in Great Britain.

OBJECTIVE: To identify health and socioeconomic factors in childhood that are precursors of unemployment in early adult life and to examine the hypothesis that young men who become unemployed are more likely to have accumulated risks to health during childhood. DESIGN: Longitudinal birth cohort study. The amount of unemployment experienced in early adult life up to age 32 years was the outcome measure used. Exposure measures to indicate vulnerability to future ill health were: height at age 7 years and the Bristol social adjustment guide (BSAG) at age 11 years, a measure of behavioural maladjustment. Socioeconomic measures were: social class at birth, crowding at age 7, qualifications attained before labour market entry, and region of residence. SETTING: Great Britain. SUBJECTS: Altogether 2256 men with complete data from the national child development study (NCDS). The NCDS has collected data on all men and women born in one week in 1958 and has followed them up using interviews, self completion questionnaires, and medical examinations at birth and at ages 7, 11, 16, 23 and 33 years. RESULTS: A total of 269 men (11.9%) experienced more than one year of unemployment between ages 22 and 32 years. Poor socioeconomic conditions in childhood and a lack of qualifications were associated with an increased risk of unemployment. Geographical region was also significant in determining the risk of unemployment. Men with short stature and poor social adjustment in childhood were more likely to experience unemployment in adult life, even after controlling for socioeconomic background, education, and parental height. These differences remained when those with chronic childhood illnesses were excluded from the analysis. The adjusted relative odds for experiencing more than one year of unemployment between ages 22 and 32 years for men who were in the top fifth of the BSAG distribution (most maladjusted) compared with those in the bottom fifth were 2.36 (95% CI 1.49, 3.73). The adjusted relative odds for experiencing more than one year of unemployment between ages 22 and 32 years for men who were in the bottom fifth of the distribution of height at age 7 years (indicating slowest growth) compared with those in the top fifth, were 2.41 (95% CI 1.43, 4.04). Adult height was not significantly associated with unemployment. CONCLUSION: The relationship between unemployment and poor health arises, in part, because men who become unemployed are more likely to have accumulated risks to health during childhood, reflected by slower growth and a greater tendency to behavioural maladjustment. Short stature in childhood is a significant indicator of poor socioeconomic circumstances in childhood and reflects earlier poor development.

Economic analysis of treating depression with nefazodone v. imipramine.

BACKGROUND: It is estimated that treating diagnosed depression costs 420 pounds million annually in England and Wales. This economic study analyses treatment of major depression with nefazodone v. imipramine. METHOD: The study updates a previously published model using data obtained from the continuation phase of a double-blind one-year placebo-controlled comparison of nefazodone with imipramine. RESULTS: Annual costs for nefazodone are lower than those for imipramine, 218 pounds compared to 254 pounds; the cost per successfully treated patient is also lower for nefazodone than for imipramine, 242 pounds v. 323 pounds. Varying the resources included in the treatment patterns still results in lower costs for nefazodone treatment. CONCLUSIONS: Based on clinical trial data for patients completing six to eight weeks of depression treatment and followed for at least one year, the model shows that the annual costs of nefazodone are lower than those for the less expensive imipramine.

The influence of different relapse criteria on the assessment of long-term efficacy of sertraline.

The treatment of depression with antidepressant agents must be continued beyond the acute phase, until the response is complete. The precise length of this continuation phase is still debated, but most authors estimate that it should last for between 4-6 months after apparent recovery. If antidepressants are withdrawn sooner, the original depression will return (relapse) in a proportion of patients. Relapse rates on placebo are high, whether patients are first-time or recurrent depressives. Most depressions are recurrent and long-term treatment therefore ensures that the changes of a new episode of illness developing are reduced. The importance of this aspect of efficacy is recognized and new antidepressants are being tested in long-term prophylactic studies. A long-term efficacy study has shown that sertraline was significantly more effective than placebo in preventing both relapse and recurrence.