Rheumatoid arthritis (RA) is an inflammatory condition that typically causes a symmetrical chronic arthritis. Timely use of disease-modifying antirheumatic drugs (DMARDs) is an essential aspect of ...disease management, but many patients may not respond even when conventional agents are used optimally.
To assess the clinical effectiveness and cost-effectiveness of adalimumab (ADA), etanercept (ETN), infliximab (IFX), rituximab (RTX) and abatacept (ABT) when used in patients with RA who have tried conventional agents and have failed to improve after trying a first tumour necrosis factor (TNF) inhibitor.
A systematic review of primary studies was undertaken. Databases searched included the Cochrane Library, MEDLINE (Ovid) and EMBASE up to July 2009.
Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria.
Data from included studies were extracted by one reviewer and checked by a second. The quality of included studies was assessed independently by two reviewers, with any disagreements resolved by discussion and consultation with a third reviewer if necessary.
Thirty-five studies were included in the systematic review: five randomised controlled trials (RCTs), one comparative study, one controlled study and 28 uncontrolled studies. One RCT (REFLEX) demonstrated the effectiveness of RTX. At 6 months significantly more patients treated with RTX achieved American College of Rheumatology (ACR) 20 relative risk (RR) = 2.85, 95% confidence interval (CI) 2.08 to 3.91 and ACR70 (RR = 12.14, 95% CI 2.96 to 49.86) compared with those treated with the placebo. Differences between groups in favour of RTX were observed at 6 months for mean change from baseline in Disease Activity Score 28 (DAS28) (mean difference -1.50, 95% CI -1.74 to -1.26) and mean change from baseline in Health Assessment Questionnaire (HAQ) score (mean difference -0.30, 95% CI -0.40 to -0.20). One RCT (ATTAIN) demonstrated the effectiveness of ABT. At 6 months significantly more patients treated with ABT achieved ACR20 (RR = 2.56, 95% CI 1.77 to 3.69) and ACR70 (RR = 6.70, 95% CI 1.62 to 27.80) compared with those treated with placebo. Significant differences between groups in favour of ABT were observed at 6 months for mean change from baseline in DAS28 score (mean difference -1.27, 95% CI -1.62 to -0.93) and mean change from baseline in HAQ score (mean difference -0.34). Twenty-eight uncontrolled studies observed improvement of effectiveness compared with before switching, in patients who switched to ADA, ETN or IFX after discontinued previous TNF inhibitor(s). Four studies were included in the systematic review of cost-effectiveness. Independent economic evaluation undertaken by the assessment group showed that compared with DMARDs, the incremental cost-effectiveness ratios (ICERs) were £34,300 per quality-adjusted life-year (QALY) for ADA, £38,800 for ETN, £36,200 for IFX, £21,200 for RTX and £38,600 for ABT. RTX dominates the TNF inhibitors and the ICER for ABT compared with RTX is over £100,000 (per QALY).
Paucity of evidence from RCTs for assessing the clinical effectiveness of TNF inhibitors and an absence of head-to-head trials comparing the five technologies.
Evidence from RCTs suggests that RTX and ABT are more effective than supportive care. Data from observational studies suggest that the use of an alternative TNF inhibitor in patients who exhibit an inadequate response to a first TNF inhibitor may offer some benefit, but there remain uncertainties with regard to the magnitude of treatment effects and their cost-effectiveness. Future research should include head-to-head trials comparing the clinical effectiveness and cost-effectiveness of the technologies against each other and emerging biologics.
This study was funded by the Health Technology Assessment programme of the National Institute for Health Research.
To identify combinations of tests and treatments to predict and prevent spontaneous preterm birth.
Searches were run on the following databases up to September 2005 inclusive: MEDLINE, EMBASE, DARE, ...the Cochrane Library (CENTRAL and Cochrane Pregnancy and Childbirth Group trials register) and MEDION. We also contacted experts including the Cochrane Pregnancy and Childbirth Group and checked reference lists of review articles and papers that were eligible for inclusion.
Two series of systematic reviews were performed: (1) accuracy of tests for the prediction of spontaneous preterm birth in asymptomatic women in early pregnancy and in women symptomatic with threatened preterm labour in later pregnancy; (2) effectiveness of interventions with potential to reduce cases of spontaneous preterm birth in asymptomatic women in early pregnancy and to reduce spontaneous preterm birth or improve neonatal outcome in women with a viable pregnancy symptomatic of threatened preterm labour. For the health economic evaluation, a model-based analysis incorporated the combined effect of tests and treatments and their cost-effectiveness.
Of the 22 tests reviewed for accuracy, the quality of studies and accuracy of tests was generally poor. Only a few tests had LR+ > 5. In asymptomatic women these were ultrasonographic cervical length measurement and cervicovaginal prolactin and fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks. In this group, tests with LR- < 0.2 were detection of uterine contraction by home uterine monitoring and amniotic fluid C-reactive protein (CRP) measurement. In symptomatic women with threatened preterm labour, tests with LR+ > 5 were absence of fetal breathing movements, cervical length and funnelling, amniotic fluid interleukin-6 (IL-6), serum CRP for predicting birth within 2-7 days of testing, and matrix metalloprotease-9, amniotic fluid IL-6, cervicovaginal fetal fibronectin and cervicovaginal human chorionic gonadotrophin (hCG) for predicting birth before 34 or 37 weeks. In this group, tests with LR- < 0.2 included measurement of cervicovaginal IL-8, cervicovaginal hCG, cervical length measurement, absence of fetal breathing movement, amniotic fluid IL-6 and serum CRP, for predicting birth within 2-7 days of testing, and cervicovaginal fetal fibronectin and amniotic fluid IL-6 for predicting birth before 34 or 37 weeks. The overall quality of the trials included in the 40 interventional topics reviewed for effectiveness was also poor. Antibiotic treatment was generally not beneficial but when used to treat bacterial vaginosis in women with intermediate flora it significantly reduced the incidence of spontaneous preterm birth. Smoking cessation programmes, progesterone, periodontal therapy and fish oil appeared promising as preventative interventions in asymptomatic women. Non-steroidal anti-inflammatory agents were the most effective tocolytic agent for reducing spontaneous preterm birth and prolonging pregnancy in symptomatic women. Antenatal corticosteroids had a beneficial effect on the incidence of respiratory distress syndrome and the risk of intraventricular haemorrhage (28-34 weeks), but the effects of repeat courses were unclear. For asymptomatic women, costs ranged from 1.08 pounds for vitamin C to 1219 pounds for cervical cerclage, whereas costs for symptomatic women were more significant and varied little, ranging from 1645 pounds for nitric oxide donors to 2555 pounds for terbutaline; this was because the cost of hospitalisation was included. The best estimate of additional average cost associated with a case of spontaneous preterm birth was approximately 15,688 pounds for up to 34 weeks and 12,104 pounds for up to 37 weeks. Among symptomatic women there was insufficient evidence to draw firm conclusions for preventing birth at 34 weeks. Hydration given to women testing positive for amniotic fluid IL-6 was the most cost-effective test-treatment combination. Indomethacin given to all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among symptomatic women. For a symptomatic woman, the most cost-effective test-treatment combination for postponing delivery by at least 48 h was the cervical length (15 mm) measurement test with treatment with indomethacin for all those testing positive. This combination was also the most cost-effective option for postponing delivery by at least 7 days. Antibiotic treatment for asymptomatic bacteriuria of all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among asymptomatic women but this does not take into account the potential side effects of antibiotics or issues such as increased resistance.
For primary prevention, an effective, affordable and safe intervention applied to all mothers without preceding testing is likely to be the most cost-effective approach in asymptomatic women in early pregnancy. For secondary prevention among women at risk of preterm labour in later pregnancy, a management strategy based on the results of testing is likely to be more cost-effective. Implementation of a treat-all strategy with simple interventions, such as fish oils, would be premature for asymptomatic women. Universal provision of high-quality ultrasound machines in labour wards is more strongly indicated for predicting spontaneous preterm birth among symptomatic women than direct management, although staffing issues and the feasibility and acceptability to mothers and health providers of such strategies need to be explored. Further research should include investigations of low-cost and effective tests and treatments to reduce and delay spontaneous preterm birth and reduce the risk of perinatal mortality arising from preterm birth.
The aim of this project was to determine the clinical effectiveness and cost-effectiveness of hysterectomy, first- and second-generation endometrial ablation (EA), and Mirena® (Bayer Healthcare ...Pharmaceuticals, Pittsburgh, PA, USA) for the treatment of heavy menstrual bleeding.
Individual patient data (IPD) meta-analysis of existing randomised controlled trials to determine the short- to medium-term effects of hysterectomy, EA and Mirena. A population-based retrospective cohort study based on record linkage to investigate the long-term effects of ablative techniques and hysterectomy in terms of failure rates and complications. Cost-effectiveness analysis of hysterectomy versus first- and second-generation ablative techniques and Mirena.
Data from women treated for heavy menstrual bleeding were obtained from national and international trials. Scottish national data were obtained from the Scottish Information Services Division.
Women who were undergoing treatment for heavy menstrual bleeding were included.
Hysterectomy, first- and second-generation EA, and Mirena.
Satisfaction, recurrence of symptoms, further surgery and costs.
Data from randomised trials indicated that at 12 months more women were dissatisfied with first-generation EA than hysterectomy odds ratio (OR): 2.46, 95% confidence interval (CI) 1.54 to 3.93; p = 0.0002), but hospital stay WMD (weighted mean difference) 3.0 days, 95% CI 2.9 to 3.1 days; p < 0.00001 and time to resumption of normal activities (WMD 5.2 days, 95% CI 4.7 to 5.7 days; p < 0.00001) were longer for hysterectomy. Unsatisfactory outcomes associated with first- and second-generation techniques were comparable 12.2% (123/1006) vs 10.6% (110/1034); OR 1.20, 95% CI 0.88 to 1.62; p = 0.2). Rates of dissatisfaction with Mirena and second-generation EA were similar 18.1% (17/94) vs 22.5% (23/102); OR 0.76, 95% CI 0.38 to 1.53; p = 0.4. Indirect estimates suggested that hysterectomy was also preferable to second-generation EA (OR 2.32, 95% CI 1.27 to 4.24; p = 0.006) in terms of patient dissatisfaction. The evidence to suggest that hysterectomy is preferable to Mirena was weaker (OR 2.22, 95% CI 0.94 to 5.29; p = 0.07). In women treated by EA or hysterectomy and followed up for a median interquartile range (IQR) duration of 6.2 (2.7-10.8) and 11.6 (7.9-14.8) years, respectively, 962/11,299 (8.5%) women originally treated by EA underwent further gynaecological surgery. While the risk of adnexal surgery was similar in both groups adjusted hazards ratio 0.80 (95% CI 0.56 to 1.15), women who had undergone ablation were less likely to need pelvic floor repair adjusted hazards ratio 0.62 (95% CI 0.50 to 0.77) and tension-free vaginal tape surgery for stress urinary incontinence adjusted hazards ratio 0.55 (95% CI 0.41 to 0.74). Abdominal hysterectomy led to a lower chance of pelvic floor repair surgery hazards ratio 0.54 (95% CI 0.45 to 0.64) than vaginal hysterectomy. The incidence of endometrial cancer following EA was 0.02%. Hysterectomy was the most cost-effective treatment. It dominated first-generation EA and, although more expensive, produced more quality-adjusted life-years (QALYs) than second-generation EA and Mirena. The incremental cost-effectiveness ratios for hysterectomy compared with Mirena and hysterectomy compared with second-generation ablation were £1440 per additional QALY and £970 per additional QALY, respectively.
Despite longer hospital stay and time to resumption of normal activities, more women were satisfied after hysterectomy than after EA. The few data available suggest that Mirena is potentially cheaper and more effective than first-generation ablation techniques, with rates of satisfaction that are similar to second-generation techniques. Owing to a paucity of trials, there is limited evidence to suggest that hysterectomy is preferable to Mirena. The risk of pelvic floor surgery is higher in women treated by hysterectomy than by ablation. Although the most cost-effective strategy, hysterectomy may not be considered an initial option owing to its invasive nature and higher risk of complications. Future research should focus on evaluation of the clinical effectivesness and cost-effectiveness of the best second-generation EA technique under local anaesthetic versus Mirena and types of hysterectomy such as laparoscopic supracervical hysterectomy versus conventional hysterectomy and second-generation EA.
The National Institute for Health Research Health Technology Assessment programme.
To establish the clinical effectiveness and cost-effectiveness of structural neuroimaging structural magnetic resonance imaging (MRI) or computed tomography (CT) scanning for all patients with ...psychosis, particularly a first episode of psychosis, relative to the current UK practice of selective screening only where it is clinically indicated.
Major electronic databases were searched from inception to November 2006.
A systematic review of studies reporting the additional diagnostic benefit of structural MRI, CT or combinations of these in patients with psychosis was conducted. The economic assessment consisted of a systematic review of economic evaluations and the development of a threshold analysis to predict the gain in quality-adjusted life-years (QALYs) required to make neuroimaging cost-effective at commonly accepted threshold levels (20,000 pounds and 30,000 pounds per QALY). Sensitivity analyses of several parameters including prevalence of psychosis were performed.
The systematic review included 24 studies of a diagnostic before-after type of design evaluating the clinical benefit of CT, structural MRI or combinations in treatment-naive, first-episode or unspecified psychotic patients, including one in schizophrenia patients resistant to treatment. Also included was a review of published case reports of misidentification syndromes. Almost all evidence was in patients aged less than 65 years. In most studies, structural neuroimaging identified very little that would influence patient management that was not suspected based on a medical history and/or physical examination and there were more incidental findings. In the four MRI studies, approximately 5% of patients had findings that would influence clinical management, whereas in the CT studies, approximately 0.5% of patients had these findings. The review of misidentification syndromes found that 25% of CT scans affected clinical management, but this may have been a selected and therefore unrepresentative sample. A threshold analysis with a 1-year time horizon was undertaken. This combined the incremental cost of routine scanning with a threshold cost per QALY value of 20,000 pounds and 30,000 pounds to predict the QoL gain required to meet these threshold values. Routine scanning versus selective scanning appears to produce different results for MRI and CT. With MRI scanning the incremental cost is positive, ranging from 37 pounds to 150 pounds; however, when scanning routinely using CT, the result is cost saving, ranging from 7 pounds to 108 pounds with the assumption of a 1% prevalence rate of tumours/cysts or other organic causes amenable to treatment. This means that for the intervention to be viewed as cost-effective, the QALY gain necessary for MRI scanning is 0.002-0.007 and with CT scanning the QALY loss that can be tolerated is between 0.0003 and 0.0054 using a 20,000 pounds threshold value. These estimates were subjected to sensitivity analysis. With a 3-month time delay, MRI remains cost-incurring with a small gain in QoL required for the intervention to be cost-effective; routine scanning with CT remains cost-saving. When the sensitivity of CT is varied to 50%, routine scanning is both cost-incurring or cost-saving depending on the scenario. Finally, the results have been shown to be sensitive to the assumed prevalence rate of brain tumours in a psychotic population.
The evidence to date suggests that if screening with structural neuroimaging was implemented in all patients presenting with psychotic symptoms, little would be found to affect clinical management in addition to that suspected by a full clinical history and neurological examination. From an economic perspective, the outcome is not clear. The strategy of neuroimaging for all is either cost-incurring or cost-saving (dependent upon whether MRI or CT is used) if the prevalence of organic causes is around 1%. However, these values are nested within a number of assumptions, and so have to be interpreted with caution. The main research priorities are to monitor the current use of structural neuroimaging in psychosis in the NHS to identify clinical triggers to its current use and subsequent outcomes; to undertake well-conducted diagnostic before-and-after studies on representative populations to determine the clinical utility of structural neuroimaging in this patient group, and to determine whether the most appropriate structural imaging modality in psychosis should be CT or MRI.
Objective To undertake a cost effectiveness analysis comparing first and second generation endometrial ablative techniques, hysterectomy, and the levonorgestrel releasing intrauterine system (Mirena) ...for treating heavy menstrual bleeding.Design Model based economic evaluation with data from an individual patient data meta-analysis supplemented with cost and outcome data from published sources taking an NHS (National Health Service) perspective. A state transition (Markov) model was developed, the structure being informed by the reviews of the trials and clinical input. A subgroup analysis, one way sensitivity analysis, and probabilistic sensitivity analysis were also carried out.Population Four hypothetical cohorts of women with heavy menstrual bleeding.Interventions One of four alternative strategies: Mirena, first or second generation endometrial ablation techniques, or hysterectomy.Main outcome measures Cost effectiveness based on incremental cost per quality adjusted life year (QALY).Results Hysterectomy is the preferred strategy for the first intervention for heavy menstrual bleeding. Although hysterectomy is more expensive, it produces more QALYs relative to other remaining strategies and is likely to be considered cost effective. The incremental cost effectiveness ratio for hysterectomy compared with Mirena is £1440 (€1633, $2350) per additional QALY. The incremental cost effectiveness ratio for hysterectomy compared with second generation ablation is £970 per additional QALY.Conclusion In light of the acceptable thresholds used by the National Institute for Health and Clinical Excellence, hysterectomy would be considered the preferred strategy for the treatment of heavy menstrual bleeding. The results concur with those of other studies but are highly sensitive to utility values used in the analysis.
To investigate the role of primary care in the management of HIV and estimate primary care-associated costs at a time of rising prevalence.
Retrospective cohort study between 1995 and 2005, using ...data from general practices contributing data to the UK General Practice Research Database. Patterns of consultation and morbidity and associated consultation costs were analysed among all practice-registered patients for whom HIV-positive status was recorded in the general practice record.
348 practices yielded 5504 person-years (py) of follow-up for known HIV-positive patients, who consult in general practice frequently (4.2 consultations/py by men, 5.2 consultations/py by women, in 2005) for a range of conditions. Consultation rates declined in the late 1990s from 5.0 and 7.3 consultations/py in 1995 in men and women, respectively, converging to rates similar to the wider population. Costs of consultation (general practitioner and nurse, combined) reflect these changes, at pound100.27 for male patients and pound117.08 for female patients in 2005. Approximately one in six medications prescribed in primary care for HIV-positive individuals has the potential for major interaction with antiretroviral medications.
HIV-positive individuals known in general practice now consult on a similar scale to the wider population. Further research should be undertaken to explore how primary care can best contribute to improving the health outcomes of this group with chronic illness. Their substantial use of primary care suggests there may be potential to develop effective integrated care pathways.
STUDY QUESTION Which of first or second generation endometrial ablative techniques, hysterectomy or the levonorgestrel intrauterine system (Mirena) is the relatively more cost effective first line ...intervention in the treatment of heavy menstrual bleeding? SUMMARY ANSWER The strategy that adopts hysterectomy as the first and only intervention produces the most quality adjusted life years (QALYs) and is likely to be considered the most cost effective strategy WHAT IS KNOWN AND WHAT THIS PAPER ADDS Less invasive alternatives to hysterectomy for the treatment of heavy menstrual bleeding, such as endometrial ablation and Mirena, have become increasing popular. Based on all available evidence on effectiveness, cost, and utility values, hysterectomy is both more costly and produces more QALYs than the available alternatives and produces cost effectiveness ratios that are likely to be accepted by decision makers.
Pi Phenotypes in Greeks Fertakis, A.; Tsourapas, A.; Douratsos, D. ...
Human heredity,
01/1974, Letnik:
24, Številka:
3
Journal Article
Recenzirano
Pi serum types were determined by starch gel electrophoresis in 504 unrelated healthy adults representative of the Greek population. Gene frequencies were as follows: PiM, 0.960; PiS, 0.028; PiZ, ...0.002; PiF, 0.006; and PiV, 0.002. No significant heterogeneity was found in this material, and distribution of Pi phenotypes is in good agreement with the Hardy-Weinberg equilibrium. PiI, PiW, PiX, and PiP alleles were not found.
Abstract
How does forced migration affect the politics of host states and, in particular, how does it impact states’ foreign policy decision-making? The relevant literature on refugee politics has ...yet to fully explore how forced migration affects host states’ behavior. One possibility is that they will employ their position in order to extract revenue from other state or nonstate actors for maintaining refugee groups within their borders. This article explores the workings of these refugee rentier states, namely states seeking to leverage their position as host states of displaced communities for material gain. It focuses on the Syrian refugee crisis, examining the foreign policy responses of three major host states—Jordan, Lebanon, and Turkey. While all three engaged in post-2011 refugee rent-seeking behavior, Jordan and Lebanon deployed a back-scratching strategy based on bargains, while Turkey deployed a blackmailing strategy based on threats. Drawing upon primary sources in English and Arabic, the article inductively examines the choice of strategy and argues that it depended on the size of the host state's refugee community and domestic elites’ perception of their geostrategic importance vis-à-vis the target. The article concludes with a discussion of these findings’ significance for understanding the international dimension of the Syrian refugee crisis and argues that they also pave the way for future research on the effects of forced displacement on host states’ political development.
In this ground-breaking work, Gerasimos Tsourapas examines how migration and political power are inextricably linked, and enhances our understanding of how authoritarian regimes rely on labour ...emigration across the Middle East and the Global South. Dr Tsourapas identifies how autocracies develop strategies to tie cross-border mobility to their own survival, highlighting domestic political struggles and the shifting regional and international landscape. In Egypt, the ruling elite has long shaped labour emigration policy in accordance with internal and external tactics aimed at regime survival. Dr Tsourapas draws on a wealth of previously-unavailable archival sources in Arabic and English, as well as extensive original interviews with Egyptian elites and policy-makers in order to produce a novel account of authoritarian politics in the Arab world. The book offers a new insight into the evolution and political rationale behind regime strategies towards migration, from Gamal Abdel Nasser's 1952 Revolution to the 2011 Arab Uprisings.
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