Cost effectiveness of home based population screening for Chlamydia trachomatis in the UK: economic evaluation of chlamydia screening studies (ClaSS) project

OBJECTIVE: To investigate the cost effectiveness of screening for Chlamydia trachomatis compared with a policy of no organised screening in the United Kingdom. DESIGN: Economic evaluation using a transmission dynamic mathematical model. SETTING: Central and southwest England. PARTICIPANTS: Hypothetical population of 50,000 men and women, in which all those aged 16-24 years were invited to be screened each year. MAIN OUTCOME MEASURES: Cost effectiveness based on major outcomes averted, defined as pelvic inflammatory disease, ectopic pregnancy, infertility, or neonatal complications. RESULTS: The incremental cost per major outcome averted for a programme of screening women only (assuming eight years of screening) was 22,300 pounds (33,000 euros; $45,000) compared with no organised screening. For a programme screening both men and women, the incremental cost effectiveness ratio was approximately 28,900 pounds. Pelvic inflammatory disease leading to hospital admission was the most frequently averted major outcome. The model was highly sensitive to the incidence of major outcomes and to uptake of screening. When both were increased the cost effectiveness ratio fell to 6200 pound per major outcome averted for screening women only. CONCLUSIONS: Proactive register based screening for chlamydia is not cost effective if the uptake of screening and incidence of complications are based on contemporary empirical studies, which show lower rates than commonly assumed. These data are relevant to discussions about the cost effectiveness of the opportunistic model of chlamydia screening being introduced in England.

Epidemiological, social, diagnostic and economic evaluation of population screening for genital chlamydial infection

OBJECTIVES: To investigate epidemiological, social, diagnostic and economic aspects of chlamydia screening in non-genitourinary medicine settings. METHODS: Linked studies around a cross-sectional population-based survey of adult men and women invited to collect urine and (for women) vulvovaginal swab specimens at home and mail these to a laboratory for testing for Chlamydia trachomatis. Specimens were used in laboratory evaluations of an amplified enzyme immunoassay (PCE EIA) and two nucleic acid amplification tests [Cobas polymerase chain reaction (PCR), Becton Dickinson strand displacement amplification (SDA)]. Chlamydia-positive cases and two negative controls completed a risk factor questionnaire. Chlamydia-positive cases were invited into a randomised controlled trial of partner notification strategies. Samples of individuals testing negative completed psychological questionnaires before and after screening. In-depth interviews were conducted at all stages of screening. Chlamydia transmission and cost-effectiveness of screening were investigated in a transmission dynamic model. SETTING AND PARTICIPANTS: General population in the Bristol and Birmingham areas of England. In total, 19,773 women and men aged 16-39 years were randomly selected from 27 general practice lists. RESULTS: Screening invitations reached 73% (14,382/19,773). Uptake (4731 participants), weighted for sampling, was 39.5% (95% CI 37.7, 40.8%) in women and 29.5% (95% CI 28.0, 31.0%) in men aged 16-39 years. Chlamydia prevalence (219 positive results) in 16-24 year olds was 6.2% (95% CI 4.9, 7.8%) in women and 5.3% (95% CI 4.4, 6.3%) in men. The case-control study did not identify any additional factors that would help target screening. Screening did not adversely affect anxiety, depression or self-esteem. Participants welcomed the convenience and privacy of home-sampling. The relative sensitivity of PCR on male urine specimens was 100% (95% CI 89.1, 100%). The combined relative sensitivities of PCR and SDA using female urine and vulvovaginal swabs were 91.8% (86.1, 95.7, 134/146) and 97.3% (93.1, 99.2%, 142/146). A total of 140 people (74% of eligible) participated in the randomised trial. Compared with referral to a genitourinary medicine clinic, partner notification by practice nurses resulted in 12.4% (95% CI -3.7, 28.6%) more patients with at least one partner treated and 22.0% (95% CI 6.1, 37.8%) more patients with all partners treated. The health service and patients costs (2005 prices) of home-based postal chlamydia screening were 21.47 pounds (95% CI 19.91 pounds, 25.99) per screening invitation and 28.56 pounds (95% CI 22.10 pounds, 30.43) per accepted offer. Preliminary modelling found an incremental cost-effectiveness ratio (2003 prices) comparing screening men and women annually to no screening in the base case of 27,000 pounds/major outcome averted at 8 years. If estimated screening uptake and pelvic inflammatory disease incidence were increased, the cost-effectiveness ratio fell to 3700 pounds/major outcome averted. CONCLUSIONS: Proactive screening for chlamydia in women and men using home-collected specimens was feasible and acceptable. Chlamydia prevalence rates in men and women in the general population are similar. Nucleic acid amplification tests can be used on first-catch urine specimens and vulvovaginal swabs. The administrative costs of proactive screening were similar to those for opportunistic screening. Using empirical estimates of screening uptake and incidence of complications, screening was not cost-effective.

Economic evaluation of varicella vaccination in Swiss children and adolescents

This study explores the effects of three different 2-dose varicella zoster virus (VZV) vaccination strategies in Switzerland. The EVITA model was used to assess clinical benefits and costs of strategies (1) vaccination of 11-15 year old adolescents with a negative or uncertain history for chickenpox, (2) universal vaccination of toddlers at age 1 to 2 years, and (3) strategy 2 plus catch-up vaccination of 11-15 year old susceptible adolescents. The cost-effectiveness analysis compares strategies 2 and 3 versus strategy 1 (current vaccination policy in Switzerland). Probabilities for clinical outcomes and medical resource utilization were derived from a real-world survey among Swiss pediatricians and general practitioners including 236 individuals with VZV infection, published information on varicella complications, and expert opinion. Costs of medical resource utilization represent official Swiss medical tariffs. The model predicts both universal childhood vaccination strategies to be more effective in reducing varicella disease burden compared to strategy 1. Economically, both universal childhood vaccination strategies with or without catch-up result in net savings from the societal perspective reflected by a benefit cost ratio (BCR) of 1.22 or 1.29, respectively. In contrast, the model predicts net costs from the payer perspective (BCR of 0.27 and 0.30, respectively). These economic findings are comparable to those reported from other similar evaluations. However, due to the recent recommendation for using a 2-dose varicella vaccination schedule, our economic results for Switzerland are somewhat less favorable than those for other country analyses in which a less expensive 1-dose vaccination regimen for toddlers has been studied.

Dexmedetomidine versus standard care sedation with propofol or midazolam in intensive care: an economic evaluation.

INTRODUCTION Dexmedetomidine was shown in two European randomized double-blind double-dummy trials (PRODEX and MIDEX) to be non-inferior to propofol and midazolam in maintaining target sedation levels in mechanically ventilated intensive care unit (ICU) patients. Additionally, dexmedetomidine shortened the time to extubation versus both standard sedatives, suggesting that it may reduce ICU resource needs and thus lower ICU costs. Considering resource utilization data from these two trials, we performed a secondary, cost-minimization analysis assessing the economics of dexmedetomidine versus standard care sedation. METHODS The total ICU costs associated with each study sedative were calculated on the basis of total study sedative consumption and the number of days patients remained intubated, required non-invasive ventilation, or required ICU care without mechanical ventilation. The daily unit costs for these three consecutive ICU periods were set to decline toward discharge, reflecting the observed reduction in mean daily Therapeutic Intervention Scoring System (TISS) points between the periods. A number of additional sensitivity analyses were performed, including one in which the total ICU costs were based on the cumulative sum of daily TISS points over the ICU period, and two further scenarios, with declining direct variable daily costs only. RESULTS Based on pooled data from both trials, sedation with dexmedetomidine resulted in lower total ICU costs than using the standard sedatives, with a difference of €2,656 in the median (interquartile range) total ICU costs-€11,864 (€7,070 to €23,457) versus €14,520 (€7,871 to €26,254)-and €1,649 in the mean total ICU costs. The median (mean) total ICU costs with dexmedetomidine compared with those of propofol or midazolam were €1,292 (€747) and €3,573 (€2,536) lower, respectively. The result was robust, indicating lower costs with dexmedetomidine in all sensitivity analyses, including those in which only direct variable ICU costs were considered. The likelihood of dexmedetomidine resulting in lower total ICU costs compared with pooled standard care was 91.0% (72.4% versus propofol and 98.0% versus midazolam). CONCLUSIONS From an economic point of view, dexmedetomidine appears to be a preferable option compared with standard sedatives for providing light to moderate ICU sedation exceeding 24 hours. The savings potential results primarily from shorter time to extubation. TRIAL REGISTRATION ClinicalTrials.gov NCT00479661 (PRODEX), NCT00481312 (MIDEX).

Screening for Chlamydia trachomatis: a systematic review of the economic evaluations and modelling

OBJECTIVE: To review systematically and critically, evidence used to derive estimates of costs and cost effectiveness of chlamydia screening. METHODS: Systematic review. A search of 11 electronic bibliographic databases from the earliest date available to August 2004 using keywords including chlamydia, pelvic inflammatory disease, economic evaluation, and cost. We included studies of chlamydia screening in males and/or females over 14 years, including studies of diagnostic tests, contact tracing, and treatment as part of a screening programme. Outcomes included cases of chlamydia identified and major outcomes averted. We assessed methodological quality and the modelling approach used. RESULTS: Of 713 identified papers we included 57 formal economic evaluations and two cost studies. Most studies found chlamydia screening to be cost effective, partner notification to be an effective adjunct, and testing with nucleic acid amplification tests, and treatment with azithromycin to be cost effective. Methodological problems limited the validity of these findings: most studies used static models that are inappropriate for infectious diseases; restricted outcomes were used as a basis for policy recommendations; and high estimates of the probability of chlamydia associated complications might have overestimated cost effectiveness. Two high quality dynamic modelling studies found opportunistic screening to be cost effective but poor reporting or uncertainty about complication rates make interpretation difficult. CONCLUSION: The inappropriate use of static models to study interventions to prevent a communicable disease means that uncertainty remains about whether chlamydia screening programmes are cost effective or not. The results of this review can be used by health service managers in the allocation of resources, and health economists and other researchers who are considering further research in this area.

Inhibition of the AKT/mTOR and erbB pathways by gefitinib, perifosine and analogs of gonadotropin-releasing hormone I and II to overcome tamoxifen resistance in breast cancer cells

Endocrine resistance in breast cancer remains a major clinical problem and is caused by crosstalk mechanisms of growth factor receptor cascades, such as the erbB and PI3K/AKT pathways. The possibilities a single breast cancer cell has to achieve resistance are manifold. We developed a model of 4-hydroxy-tamoxifen (OHT)‑resistant human breast cancer cell lines and compared their different expression patterns, activation of growth factor receptor pathways and compared cells by genomic hybridization (CGH). We also tested a panel of selective inhibitors of the erbB and AKT/mTOR pathways to overcome OHT resistance. OHT‑resistant MCF-7-TR and T47D-TR cells showed increased expression of HER2 and activation of AKT. T47D-TR cells showed EGFR expression and activated MAPK (ERK-1/2), whereas in resistant MCF-7-TR cells activated AKT was due to loss of CTMP expression. CGH analyses revealed remarkable aberrations in resistant sublines, which were predominantly depletions. Gefitinib inhibited erbB signalling and restored OHT sensitivity in T47D-TR cells. The AKT inhibitor perifosine restored OHT sensitivity in MCF-7-TR cells. All cell lines showed expression of receptors for gonadotropin-releasing hormone (GnRH) I and II, and analogs of GnRH-I/II restored OHT sensitivity in both resistant cell lines by inhibition of erbB and AKT signalling. In conclusion, mechanisms to escape endocrine treatment in breast cancer share similarities in expression profiling but are based on substantially different genetic aberrations. Evaluation of activated mediators of growth factor receptor cascades is helpful to predict response to specific inhibitors. Expression of GnRH-I/II receptors provides multi-targeting treatment strategies.

Cumulative costs for the prosthetic reconstructions and maintenance in young adult patients with birth defects affecting the formation of teeth

OBJECTIVES: To assess retrospectively the cumulative costs for the long-term oral rehabilitation of patients with birth defects affecting the development of teeth. METHODS: Patients with birth defects who had received fixed reconstructions on teeth and/or implants > or =5 years ago were asked to participate in a comprehensive clinical, radiographic and economic evaluation. RESULTS: From the 45 patients included, 18 were cases with a cleft lip and palate, five had amelogenesis/dentinogenesis imperfecta and 22 were cases with hypodontia/oligodontia. The initial costs for the first oral rehabilitation (before the age of 20) had been covered by the Swiss Insurance for Disability. The costs for the initial rehabilitation of the 45 cases amounted to 407,584 CHF (39% for laboratory fees). Linear regression analyses for the initial treatment costs per replaced tooth revealed the formula 731 CHF+(811 CHF x units) on teeth and 3369 CHF+(1183 CHF x units) for reconstructions on implants (P<.001). Fifty-eight percent of the patients with tooth-supported reconstructions remained free from failures/complications (median observation 15.7 years). Forty-seven percent of the patients with implant-supported reconstructions remained free from failures/complications (median observation 8 years). The long-term cumulative treatment costs for implant cases, however, were not statistically significantly different compared with cases reconstructed with tooth-supported fixed reconstructions. Twenty-seven percent of the initial treatment costs were needed to cover supportive periodontal therapy as well as the treatment of technical/biological complications and failures. CONCLUSION: Insurance companies should accept to cover implant-supported reconstructions because there is no need to prepare healthy teeth, fewer tooth units need to be replaced and the cumulative long-term costs seem to be similar compared with cases restored on teeth.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Genetic evaluation of short stature

After a proper medical history, growth analysis and physical examination of a short child, followed by radiological and laboratory screening, the clinician may decide to perform genetic testing. We propose several clinical algorithms that can be used to establish the diagnosis. GH1 and GHRHR should be tested in children with severe isolated growth hormone deficiency and a positive family history. A multiple pituitary dysfunction can be caused by defects in several genes, of which PROP1 and POU1F1 are most common. GH resistance can be caused by genetic defects in GHR, STAT5B, IGF1, IGFALS, which all have their specific clinical and biochemical characteristics. IGF-I resistance is seen in heterozygous defects of the IGF1R. If besides short stature additional abnormalities are present, these should be matched with known dysmorphic syndromes. If no obvious candidate gene can be determined, a whole genome approach can be taken to check for deletions, duplications and/or uniparental disomies.

Excellent agreement between genetic and hydrogen breath tests for lactase deficiency and the role of extended symptom assessment

Clinical manifestations of lactase (LCT) deficiency include intestinal and extra-intestinal symptoms. Lactose hydrogen breath test (H2-BT) is considered the gold standard to evaluate LCT deficiency (LD). Recently, the single-nucleotide polymorphism C/T(-13910) has been associated with LD. The objectives of the present study were to evaluate the agreement between genetic testing of LCT C/T(-13910) and lactose H2-BT, and the diagnostic value of extended symptom assessment. Of the 201 patients included in the study, 194 (139 females; mean age 38, range 17-79 years, and 55 males, mean age 38, range 18-68 years) patients with clinical suspicion of LD underwent a 3-4 h H2-BT and genetic testing for LCT C/T(-13910). Patients rated five intestinal and four extra-intestinal symptoms during the H2-BT and then at home for the following 48 h. Declaring H2-BT as the gold standard, the CC(-13910) genotype had a sensitivity of 97% and a specificity of 95% with a of 0.9 in diagnosing LCT deficiency. Patients with LD had more intense intestinal symptoms 4 h following the lactose challenge included in the H2-BT. We found no difference in the intensity of extra-intestinal symptoms between patients with and without LD. Symptom assessment yielded differences for intestinal symptoms abdominal pain, bloating, borborygmi and diarrhoea between 120 min and 4 h after oral lactose challenge. Extra-intestinal symptoms (dizziness, headache and myalgia) and extension of symptom assessment up to 48 h did not consistently show different results. In conclusion, genetic testing has an excellent agreement with the standard lactose H2-BT, and it may replace breath testing for the diagnosis of LD. Extended symptom scores and assessment of extra-intestinal symptoms have limited diagnostic value in the evaluation of LD.

Is hatchery stocking a help or harm? Evidence, limitations and future directions in ecological and genetic surveys

Hatchery fish stocking for stock enhancement has been operated at a massive and global scale. However, the use of hatchery fish as a means of stock enhancement is highly controversial, and little is known about its effects on wild stock and consequences for stock enhancement. Here we review the scientific literature on this subject in order to address a fundamental - question is hatchery stocking a help or harm for wild stock and stock enhancement? We summarized 266 peer-reviewed papers that were published in the last 50 years, which describe empirical case studies on ecology and genetics of hatchery stocks and their effects on stock enhancement. Specifically, we asked whether hatchery stock and wild stock differed in fitness and the level of genetic variation, and whether stocking affected population abundance. Seventy studies contained comparisons between hatchery and wild stocks, out of which 23 studies showed significantly negative effects of hatchery rearing on the fitness of stocked fish, and 28 studies showed reduced genetic variation in hatchery populations. None of these studies suggested a positive genetic effect on the fitness of hatchery-reared individuals after release. These results suggest that negative effects of hatchery rearing are not just a concern but undeniably present in many aquaculture species. In a few cases, however, no obvious effect of hatchery rearing was observed, and a positive contribution of hatchery stock to the abundance of fish populations was indicated. These examples suggest that there is a chance to improve hatchery practices and mitigate the negative effects on wild stocks, although scientific data supporting the positive effect on stock enhancement are largely missing at this moment. Technically, microsatellite-based parentage assignments have been proven as a useful tool for the evaluation of reproductive fitness in natural settings, which is a key for stock enhancement by hatchery-based stocking. We discuss implications of these results, as well as their limitations and future directions. (C) 2010 Elsevier B.V. All rights reserved.

Genetic evidence supporting the association of protease and protease inhibitor genes with inflammatory bowel disease: a systematic review

As part of the European research consortium IBDase, we addressed the role of proteases and protease inhibitors (P/PIs) in inflammatory bowel disease (IBD), characterized by chronic mucosal inflammation of the gastrointestinal tract, which affects 2.2 million people in Europe and 1.4 million people in North America. We systematically reviewed all published genetic studies on populations of European ancestry (67 studies on Crohn's disease [CD] and 37 studies on ulcerative colitis [UC]) to identify critical genomic regions associated with IBD. We developed a computer algorithm to map the 807 P/PI genes with exact genomic locations listed in the MEROPS database of peptidases onto these critical regions and to rank P/PI genes according to the accumulated evidence for their association with CD and UC. 82 P/PI genes (75 coding for proteases and 7 coding for protease inhibitors) were retained for CD based on the accumulated evidence. The cylindromatosis/turban tumor syndrome gene (CYLD) on chromosome 16 ranked highest, followed by acylaminoacyl-peptidase (APEH), dystroglycan (DAG1), macrophage-stimulating protein (MST1) and ubiquitin-specific peptidase 4 (USP4), all located on chromosome 3. For UC, 18 P/PI genes were retained (14 proteases and 4 protease inhibitors), with a considerably lower amount of accumulated evidence. The ranking of P/PI genes as established in this systematic review is currently used to guide validation studies of candidate P/PI genes, and their functional characterization in interdisciplinary mechanistic studies in vitro and in vivo as part of IBDase. The approach used here overcomes some of the problems encountered when subjectively selecting genes for further evaluation and could be applied to any complex disease and gene family.

Diagnostic accuracy of magnetic resonance imaging: a prospective evaluation of patients with suspected appendicitis (diamond)

To show the effect of standard magnetic resonance imaging (MRI) in patients with suspected appendicitis on negative laparotomy and perforation rate. Moreover, the economic impact on hospital resources was evaluated.

Comparison of genetic gains per year for carcass traits among breeding programs in the Japanese Brown and the Japanese Black cattle

The breeding program for beef cattle in Japan has changed dramatically over 4 decades. Visual judging was done initially, but progeny testing in test stations began in 1968. In the 1980s, the genetic evaluation program using field records, so-called on-farm progeny testing, was first adopted in Oita, Hyogo, and Kumamoto prefectures. In this study, genetic trends for carcass traits in these 3 Wagyu populations were estimated, and genetic gains per year were compared among the 3 different beef cattle breeding programs. The field carcass records used were collected between 1988 and 2003. The traits analyzed were carcass weight, LM area, rib thickness, s.c. fat thickness, and beef marbling standard number. The average breeding values of reproducing dams born the same year were used to estimate the genetic trends for the carcass traits. For comparison of the 3 breeding programs, birth years of the dams were divided into 3 periods reflecting each program. Positive genetic trends for beef marbling standard number were clearly shown in all populations. The genetic gains per year for all carcass traits were significantly enhanced by adopting the on-farm progeny testing program. These results indicate that the on-farm progeny testing program with BLUP is a very powerful approach for genetic improvement of carcass traits in Japanese Wagyu beef cattle.