Breastfeeding promotion for infants in neonatal units: a systematic review.

BACKGROUND: Breastfeeding/breastmilk feeding of infants in neonatal units is vital to the preservation of short- and long-term health, but rates are very low in many neonatal units internationally. The aim of this review was to evaluate the effectiveness of clinical, public health and health promotion interventions that may promote or inhibit breastfeeding/breastmilk feeding for infants admitted to neonatal units. METHODS: Systematic review with narrative synthesis. Studies were identified from structured searches of 19 electronic databases from inception to February 2008; hand searching of bibliographies; Advisory Group members helped identify additional sources. INCLUSION CRITERIA: controlled studies of interventions intended to increase breastfeeding/feeding with breastmilk that reported breastmilk feeding outcomes and included infants admitted to neonatal units, their mothers, families and caregivers. Data were extracted and appraised for quality using standard processes. Study selection, data extraction and quality assessment were independently checked. Study heterogeneity prevented meta-analysis. RESULTS: Forty-eight studies were identified, mainly measuring short-term outcomes of single interventions in stable infants. We report here a sub-set of 21 studies addressing interventions tested in at least one good-quality or more than one moderate-quality study. Effective interventions identified included kangaroo skin-to-skin contact, simultaneous milk expression, peer support in hospital and community, multidisciplinary staff training, and Unicef Baby Friendly accreditation of the associated maternity hospital. CONCLUSIONS: Breastfeeding/breastmilk feeding is promoted by close, continuing skin-to-skin contact between mother and infant, effective breastmilk expression, peer support in hospital and community, and staff training. Evidence gaps include health outcomes and costs of intervening with less clinically stable infants, and maternal health and well-being. Effects of public health and policy interventions and the organization of neonatal services remain unclear. Infant feeding in neonatal units should be included in public health surveillance and policy development; relevant definitions are proposed.

Population tobacco control interventions and their effects on social inequalities in smoking: systematic review.

OBJECTIVE: To assess the effects of population tobacco control interventions on social inequalities in smoking. DATA SOURCES: Medical, nursing, psychological, social science and grey literature databases, bibliographies, hand-searches and contact with authors. STUDY SELECTION: Studies were included (n = 84) if they reported the effects of any population-level tobacco control intervention on smoking behaviour or attitudes in individuals or groups with different demographic or socioeconomic characteristics. DATA EXTRACTION: Data extraction and quality assessment for each study were conducted by one reviewer and checked by a second. DATA SYNTHESIS: Data were synthesised using graphical ("harvest plot") and narrative methods. No strong evidence of differential effects was found for smoking restrictions in workplaces and public places, although those in higher occupational groups may be more likely to change their attitudes or behaviour. Smoking restrictions in schools may be more effective in girls. Restrictions on sales to minors may be more effective in girls and younger children. Increasing the price of tobacco products may be more effective in reducing smoking among lower-income adults and those in manual occupations, although there was also some evidence to suggest that adults with higher levels of education may be more price-sensitive. Young people aged under 25 are also affected by price increases, with some evidence that boys and non-white young people may be more sensitive to price. CONCLUSIONS: Population-level tobacco control interventions have the potential to benefit more disadvantaged groups and thereby contribute to reducing health inequalities.

Etanercept and infliximab for the treatment of psoriatic arthritis: a systematic review and economic evaluation.

OBJECTIVES: To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and infliximab for the treatment of active and progressive psoriatic arthritis (PsA) in patients who have inadequate response to standard treatment, including disease-modifying antirheumatic drug (DMARD) therapy. DATA SOURCES: Electronic databases were searched up to July 2004. REVIEW METHODS: A systematic review evaluated the clinical efficacy and adverse effects of etanercept and infliximab. The efficacy of DMARDs in the treatment of PsA was also reviewed and treatments were compared using Bayesian evidence synthesis methods. Following evaluation of existing economic evaluations of etanercept and infliximab in PsA, a new economic model was developed (the York Model). This utilised the results from the evidence synthesis and data from a range of other sources. RESULTS: Across the two trials, at 12 weeks, around 65% of patients treated with etanercept achieved an American College of Rheumatology (ACR) 20 {pooled relative risk (RR) 4.19 [95% confidence interval (CI) 2.74 to 6.42]}, demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. In addition, around 45% of patients treated with etanercept achieved an ACR 50 [pooled RR 10.84 (95% CI 4.47 to 26.28)] and around 12% achieved an ACR 70 [pooled RR 16.28 (95% CI 2.20 to 120.54)], demonstrating a good level of efficacy. The subgroup analyses conducted in one trial revealed that the effect of etanercept was not dependent upon patients' concomitant use of methotrexate. In addition, almost 85% of patients treated with etanercept achieved a Psoriatic Arthritis Response Criteria (PsARC) [pooled RR 2.60 (95% CI 1.96 to 3.45). The Psoriatic Area and Severity Index (PASI) results indicate some beneficial effect on psoriasis at 12 weeks; however, the data are sparse. The statistically significant reduction (improvement) in Health Assessment Questionnaire (HAQ) score with etanercept compared with placebo indicates a beneficial effect of etanercept on function. Similar results were seen at 24 weeks, except that the results for PASI 75 and PASI 50 now achieved statistical significance and data for Total Sharp Score annualised rate of progression were available; this was statistically significantly lower in etanercept-treated patients than in placebo-treated patients. Uncontrolled follow-up of patients indicates that treatment benefit may be maintained for at least 50 weeks. At 16 weeks, 65% of patients treated with infliximab achieved an ACR 20 [RR 6.80 (95% CI 2.89 to 16.01)], demonstrating a basic degree of efficacy in terms of arthritis-related symptoms. This level of efficacy was not dependent upon patients' concomitant use of methotrexate. Almost half the patients treated with infliximab achieved an ACR 50 [RR 49.00 (95% CI 3.06 to 785.06)] and over one-quarter achieved an ACR 70 [RR 31.00 (95% CI 1.90 to 504.86)] compared with none of the placebo group, demonstrating a good level of efficacy. In addition, 75% of patients treated with infliximab achieved a PsARC [RR 3.55 (95% CI 2.05 to 6.13)]. The beneficial treatment effect on psoriasis was also statistically significant with a mean difference in percentage change from baseline in PASI of -5 (95% CI -6.8 to -3.3), as was the percentage improvement from baseline in HAQ score with infliximab compared with placebo [mean difference 51.4 (95% CI 48.08 to 54.72)], indicating a beneficial effect of infliximab on functional status. Uncontrolled data from all measures of joint disease, psoriasis and HAQ collected up to 50 weeks of follow-up reflect those at 16 weeks. There were no radiographic assessments, so nothing can be determined about the potential or otherwise of infliximab to delay the progression of joint disease. Using the York cost-effectiveness model, infliximab was consistently dominated by etanercept because of its higher acquisition and administration costs without superior effectiveness. The incremental cost per quality-adjusted life-year (QALY) gained of etanercept compared with palliative care ranged from 14,818 pounds (females, 40-year time horizon) to 49,374 pounds (males, 1-year time horizon) if it is assumed that, when patients eventually fail on biological therapy, their disability (in terms of HAQ score) deteriorates by the same amount as it improved when they initially respond to treatment (rebound equal to gain). Results for etanercept ranged from 25,443 pounds (females, 40-year time horizon) to 49,441 pounds (males, 1-year time horizon) per QALY gained under the assumption that, when patients fail on therapy, their disability level returns to what it would have been had they never responded (rebound equal to natural history). CONCLUSIONS: The limited data available indicated that etanercept and infliximab are efficacious in the treatment of PsA with beneficial effects on both joint and psoriasis symptoms and on functional status. Short-term data indicated that etanercept can delay joint disease progression, but long-term data are needed. There are no controlled data as yet to indicate that infliximab can delay joint disease progression. Treatment with both etanercept and infliximab for 12 weeks demonstrated a significant degree of efficacy, with no statistically significant difference between them. For both drugs, adverse events were common with mild injection/infusion reactions being the main treatment-related effect. The York model indicated that etanercept is more cost-effective than infliximab as it has a lower cost with little difference in outcomes. The cost-effectiveness of etanercept is also sensitive to assumptions made about the extent of disease progression when patients are responding to therapy. The number of years for which a patient can be safely on biologicals is uncertain so these results should be considered with caution. Further research should include long-term controlled trials to confirm benefits, review adverse events and to explore further the implications of biologic therapy.

Systematic review of water fluoridation.

OBJECTIVE: To review the safety and efficacy of fluoridation of drinking water. DESIGN: Search of 25 electronic databases and world wide web. Relevant journals hand searched; further information requested from authors. Inclusion criteria were a predefined hierarchy of evidence and objectives. Study validity was assessed with checklists. Two reviewers independently screened sources, extracted data, and assessed validity. MAIN OUTCOME MEASURES: Decayed, missing, and filled primary/permanent teeth. Proportion of children without caries. Measure of effect was the difference in change in prevalence of caries from baseline to final examination in fluoridated compared with control areas. For potential adverse effects, all outcomes reported were used. RESULTS: 214 studies were included. The quality of studies was low to moderate. Water fluoridation was associated with an increased proportion of children without caries and a reduction in the number of teeth affected by caries. The range (median) of mean differences in the proportion of children without caries was -5.0% to 64% (14.6%). The range (median) of mean change in decayed, missing, and filled primary/permanent teeth was 0.5 to 4.4 (2.25) teeth. A dose-dependent increase in dental fluorosis was found. At a fluoride level of 1 ppm an estimated 12.5% (95% confidence interval 7.0% to 21.5%) of exposed people would have fluorosis that they would find aesthetically concerning. CONCLUSIONS: The evidence of a beneficial reduction in caries should be considered together with the increased prevalence of dental fluorosis. There was no clear evidence of other potential adverse effects.

A systematic review and economic evaluation of new-generation computed tomography scanners for imaging in coronary artery disease and congenital heart disease: Somatom Definition Flash, Aquilion ONE, Brilliance iCT and Discovery CT750 HD.

BACKGROUND: Computed tomography (CT) is important in diagnosing and managing many conditions, including coronary artery disease (CAD) and congenital heart disease. Current CT scanners can very accurately diagnose CAD requiring revascularisation in most patients. However, imaging technologies have developed rapidly and new-generation computed tomography (NGCCT) scanners may benefit patients who are difficult to image (e.g. obese patients, patients with high or irregular heart beats and patients who have high levels of coronary calcium or a previous stent or bypass graft). OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of NGCCT for diagnosing clinically significant CAD in patients who are difficult to image using 64-slice computed tomography and treatment planning in complex congenital heart disease. DATA SOURCES: Bibliographic databases were searched from 2000 to February/March 2011, including MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA) database and Science Citation Index (SCI). Trial registers and conference proceedings were searched. REVIEW METHODS: Systematic review methods followed published guidance. Risk of bias was assessed using QUADAS-2. Results were stratified by patient group. Summary sensitivity and specificity were calculated using a bivariate summary receiver operating characteristic, or random effects model. Heterogeneity was assessed using the chi-squared statistic and I(2)-statistic. Cost-effectiveness of NGCCT was modelled separately for suspected and known CAD, evaluating invasive coronary angiography (ICA) only, ICA after positive NGCCT (NGCCT-ICA), and NGCCT only. The cost-effectiveness of NGCCT, compared with 64-slice CT, in reducing imaging-associated radiation in congenital heart disease was assessed. RESULTS: Twenty-four studies reported accuracy of NGCCT for diagnosing CAD in difficult-to-image patients. No clinical effectiveness studies of NGCCT in congenital heart disease were identified. The pooled per-patient estimates of sensitivity were 97.7% [95% confidence interval (CI) 88.0% to 99.9%], 97.7% (95% CI 93.2% to 99.3%) and 96.0% (95% CI 88.8% to 99.2%) for patients with arrhythmias, high heart rates and previous stent, respectively. The corresponding estimates of specificity were 81.7% (95% CI 71.6% to 89.4%), 86.3% (95% CI 80.2% to 90.7%) and 81.6% (95% CI 74.7% to 87.3%), respectively. In patients with high coronary calcium scores, previous bypass grafts or obesity, only per-segment or per-artery data were available. Sensitivity estimates remained high (> 90% in all but one study). In patients with suspected CAD, the NGCCT-only strategy appeared most cost-effective; the incremental cost-effectiveness ratio (ICER) of NGCCT-ICA compared with NGCCT only was £71,000. In patients with known CAD, the most cost-effective strategy was NGCCT-ICA (highest cost saving, dominates ICA only). The ICER of NGCCT only compared with NGCCT-ICA was £726,230. For radiation exposure only, the ICER for NGCCT compared with 64-slice CT in congenital heart disease ranged from £521,000 for the youngest patients to £90,000 for adults. LIMITATIONS: Available data were limited, particularly for obese patients and patients with previous bypass grafts. All studies of the accuracy of NGCCT assume that the reference standard (ICA) is 100% sensitive and specific; however, there is some evidence that ICA may sometimes underestimate the extent and severity of stenosis. Patients with more than one criterion that could contribute to difficulty in imaging were often excluded from studies; the effect on test accuracy of multiple difficult to image criteria remains uncertain. CONCLUSIONS: NGCCT may be sufficiently accurate to diagnose clinically significant CAD in some or all difficult-to-image patient groups. Economic analyses suggest that NGCCT is likely to be considered cost-effective for difficult-to-image patients with CAD, at current levels of willingness to pay in the NHS. For patients with suspected CAD, NGCCT only would be most favourable; for patients with known CAD, NGCCT-ICA would be most favourable. No studies assessing the effects of NGCCT on therapeutic decision making, or subsequent patient outcomes, were identified. The ideal study to address these questions would be a large multi-centre RCT. However, one possible alternative might be to establish a multicentre tracker study. High-quality test accuracy studies, particularly in obese patients, patients with high coronary calcium, and those with previous bypass grafts are needed to confirm the findings of our systematic review. These studies should include patients with multiple difficult to image criteria. FUNDING: The National Institute for Health Research Health Technology Assessment programme. This project was funded by the HTA programme, on behalf of NICE, as project number 10/107/01.

Contrast-enhanced ultrasound using SonoVue® (sulphur hexafluoride microbubbles) compared with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging for the characterisation of focal liver lesions and detection of liver metastases: a systematic review and cost-effectiveness analysis.

BACKGROUND: Medical imaging techniques are important in the management of many patients with liver disease. Unenhanced ultrasound examinations sometimes identify focal abnormalities in the liver that may require further investigation, primarily to distinguish liver cancers from benign abnormalities. One important factor in selecting an imaging test is the ability to provide a rapid diagnosis. Options for additional imaging investigations include computed tomography (CT) and/or magnetic resonance imaging (MRI) and biopsy when the diagnosis remains uncertain. CT and MRI usually require referral with associated waiting time and are sometimes contraindicated. The use of contrast agents may improve the ability of ultrasound to distinguish between liver cancer and benign abnormalities and, because it can be performed at the same appointment as unenhanced ultrasound, more rapid diagnoses may be possible. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of contrast-enhanced ultrasound (CEUS) using SonoVue(®) with that of contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI) for the assessment of adults with focal liver lesions (FLLs) in whom previous liver imaging is inconclusive. DATA SOURCES: Eight bibliographic databases including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from 2000 to September/October 2011. Research registers and conference proceedings were also searched. REVIEW METHODS: Systematic review methods followed published guidance. Risk of bias was assessed using a modified version of the QUADAS-2 tool. Results were stratified by clinical indication for imaging (characterisation of FLLs detected on ultrasound surveillance of cirrhosis patients, detection of liver metastases, characterisation of incidentally detected FLLs, assessment of treatment response). For incidental FLLs, pooled estimates of sensitivity and specificity, with 95% CIs, were calculated using a random-effects model. For other clinical indications a narrative summary was used. The cost-effectiveness of CEUS was modelled separately for the three main clinical applications considered [characterisation of FLLs detected on ultrasound surveillance of cirrhosis patients, detection of liver metastases in patients with colorectal cancer (CRC), characterisation of incidentally detected FLLs]. RESULTS: Of the 854 references identified, 19 (describing 18 studies) were included in the review. Hand searching of conference proceedings identified a further three studies. Twenty of the 21 studies included in the systematic review were diagnostic test accuracy studies. Studies in cirrhosis patients reported varying estimates of test performance. There was no consistent evidence of a significant difference in performance between imaging modalities. It was unclear whether or not CEUS alone is adequate to rule out hepatocellular carcinoma (HCC) for FLLs of < 30 mm; one study indicated that CEUS may be better at ruling out HCC for FLLs of 11-30 mm [very small FLLs (< 10 mm) excluded]. There was no consistent evidence of a difference in test performance between imaging modalities for the detection of metastases; CEUS alone may be adequate to rule out liver metastases in colorectal cancer. In patients with incidentally detected FLLs, the pooled estimates of sensitivity for any malignancy using CEUS and CECT were 95.1% and 94.6%, respectively, and the corresponding specificity estimates were 93.8% and 93.1% respectively. One study comparing CEUS with CEMRI reported similar sensitivity and lower specificity for both modalities. In the surveillance of cirrhosis, CEUS was as effective as but £379 less costly than CECT. CEMRI was £1063 more costly than CEUS and gained 0.022 QALYs. In the detection of liver metastases from CRC, CEUS cost £1 more than CECT, and at a lifetime time horizon they yielded equal QALYs. CEMRI was dominated by CECT. In the characterisation of incidentally detected FLLs, CEUS was slightly more effective than CECT and CEMRI (by 0.0002 QALYs and 0.0026 QALYs respectively) and less costly (by £52 and £131 respectively). LIMITATIONS: There were a number of methodological issues specific to the studies included in this review. The main indication for liver imaging in the populations considered is likely to be to rule out primary liver cancer or metastases. Therefore, patient-level analyses of test performance are of particular interest. Some of the studies included in this review reported per-patient analyses; however, no study clearly stated how results were defined (e.g. was the presence of any positive lesion regarded as a positive test for the whole patient). In addition, a number of studies reported data for one lesion per patient (treated as per-patient data in this assessment). These studies generally selected the largest lesion or the lesion 'most suspicious for malignancy' for inclusion in analyses, with the consequence that estimates of test performance may have been exaggerated. The applicability of studies included in this review may be limited, as the majority of imaging studies were interpreted by multiple, experienced operators and the prevalence of malignancy in included studies appeared higher than might be expected in clinical practice. The cost-effectiveness analyses did not take into account the potential benefits of reduced anxiety that may arise from potentially shorter waiting times associated with SonoVue CEUS. CONCLUSIONS: SonoVue CEUS could provide similar diagnostic performance to other imaging modalities (CECT and CEMRI) for the assessment of FLLs. Economic analyses indicated that CEUS was a cost-effective replacement for CEMRI. The use of CEUS instead of CECT was considered cost-effective in the surveillance of cirrhosis and the characterisation of incidentally detected FLLs, with similar costs and effects for the detection of liver metastases from CRC. Further research is needed to compare the effects of different imaging modalities (SonoVue CEUS, CECT, CEMRI) on therapeutic planning, treatment and clinical outcomes. Future test accuracy studies should provide standardised definitions of a positive imaging test, and compare all three imaging modalities in the same patient group. STUDY REGISTRATION: PROSPERO: CRD42011001694. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A systematic review and cost-effectiveness analysis of specialist services and adrenaline auto-injectors in anaphylaxis.

BACKGROUND: Anaphylaxis is a severe, life-threatening generalised or systemic hypersensitivity reaction with high mortality. Specialist services (SSs) are believed to reduce anaphylaxis recurrence and improve use of adrenaline injectors (AIs), which can reduce mortality if used correctly and in time. OBJECTIVES: To review the evidence on which persons are at high risk of anaphylactic episodes, the effects of history-taking (including signs, symptoms and physical examination) for anaphylaxis, and when (suspected) patients should be referred. To assess the cost-effectiveness of SS compared with standard care (SC) with or without prescription of AIs. DATA SOURCES: In order to assess the clinical effectiveness, 10 databases [Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), NHS Economic Evaluation Database (NHS EED), Science Citation Index (SCI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, from inception up to March 2011] were searched without data restriction in order to identify relevant studies [randomised controlled trials (RCTs), controlled clinical trials, observational studies, prognostic studies using a multivariate model] written in English. REVIEW METHODS: Standard review methods were applied for the assessment of clinical effectiveness. A Markov model, validated by clinical experts, was constructed, which modelled anaphylaxis according to trigger: either food, drug, insect or idiopathic. Anaphylaxis mortality was modelled as a function of time to die and time for emergency response. Probabilistic sensitivity analysis on key parameters was performed. RESULTS: From the systematic review, 11,058 references were identified by the searches for studies assessing the clinical effectiveness. In total, 107 papers were obtained, and five prospective observational studies, including 1725 patients, were included. These studies estimated the risk of recurrence to be between 30% and 42.8%. In children (< 12 years), an overall recurrence of 27% was reported, with food being the most frequent allergen (71%). From the cost-effectiveness analysis (CEA), SC with injectors was dominated by SS with or without injectors. SS with no injectors would be cost-effective if the threshold for a quality-adjusted life-year (QALY) was greater than about £ 740 and with injectors would be cost-effective if the threshold was > £ 1800. These results were robust to all sensitivity analyses except at relatively extreme values of a small number of parameters. LIMITATIONS: Limitations of the study include the low yield from the systematic review; in particular there were no good-quality studies of either SSs or AI effectiveness. This implied a great reliance on expert opinion in the CEA. However, this was appropriately addressed using sensitivity analysis. CONCLUSIONS: Only five observational studies assessing clinical effectiveness were identified. Owing to the lack of good data to inform the effectiveness of anaphylaxis intervention, we recommend considerations of RCTs or at least well-designed observational studies of the components of care in SSs. The results of the CEA showed that SS with AIs was cost-effective at a threshold of £ 20,000 per QALY. More well-designed prospective studies on the effectiveness of SSs are needed to confirm these findings.

Treatment with tirofiban for acute coronary syndrome (ACS): a systematic review and network analysis.

OBJECTIVE: To assess the efficacy of tirofiban in comparison to usual care or other GPIIb/IIIa antagonists (eptifibatide and abciximab). Results were analysed by drug administration with planned percutaneous coronary intervention (PCI) or as medical management without planned PCI, and separately for STEMI or NSTE ACS patients. RESEARCH DESIGN AND METHODS: A systematic review was performed of randomized controlled trials of tirofiban, abciximab, eptifibatide or usual care given to patients with acute coronary syndrome. Nine databases were searched up to March 2010. Pair-wise meta-analysis was used to combine all available direct comparisons; indirect comparisons and network analysis were performed when this was not possible. The primary outcome was MACE (major adverse cardiac event). RESULTS: The search yielded 8, 119 records and 50 trials were included (total number of patients = 52,958). Compared to usual care, high and medium-dose tirofiban (25 and 10 µg/kg/min) administered with planned PCI reduced MACE at 30 days for patients with STEMI (RR 0.67, 95% CI 0.45, 0.99; RR 0.28, 95% CI 0.10, 0.80), but was not effective as a medical management. Medium-dose tirofiban (10 µg/kg/min) administered with planned PCI or low dose (0.4 µg/kg/min) as medical management reduced the risk of MACE for patients with NSTE ACS (RR 0.39, 95% CI 0.21, 0.75; RR 0.58, 95% CI 0.41, 0.83) in comparison to usual care, but at the expense of increased thrombocytopenia (RR 3.26, 95% CI 1.31, 8.13). Evidence from RCTs and network analysis indicated tirofiban and abciximab were equally effective and safe. Comparing tirofiban and eptifibatide treatment by indirect and network analysis produced inconclusive results. CONCLUSIONS: Tirofiban was more effective than usual care for STEMI and NSTE ACS patients receiving planned PCI, and NSTE ACS patients receiving medical management. Tirofiban and abciximab were equally effective. Comparisons of tirofiban and eptifibatide were inconclusive.

Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of topotecan in combination with cisplatin for the treatment of recurrent and stage IVB carcinoma of the cervix, in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcomes measured were overall survival, progression-free survival, response rates, adverse effects of treatment, health-related quality of life (HRQoL) and quality-adjusted life-years (QALYs) gained. The manufacturer stated that topotecan plus cisplatin is the only combination regimen to date to have demonstrated a statistically significant survival advantage compared to cisplatin monotherapy in the licensed population. The clinical evidence came from three clinical trials comparing topotecan plus cisplatin with cisplatin monotherapy (GOG-0179), topotecan plus cisplatin with paclitaxel plus cisplatin (GOG-0169), and four cisplatin-based combination therapies: topotecan plus cisplatin, paclitaxel plus cisplatin, gemcitabine plus cisplatin, and vinorelbine plus cisplatin (GOG-0204). Results from GOG-0179 showed greater median overall survival with topotecan plus cisplatin than with cisplatin monotherapy: 9.4 months versus 6.5 months. Similar results were also reported for median progression-free survival. Response rates also showed an advantage with topotecan plus cisplatin compared with cisplatin monotherapy. The response rates in patients receiving cisplatin monotherapy were very low, but the potential reasons for this were not discussed in the manufacturer's submission. Patients receiving topotecan plus cisplatin experienced a greater number of adverse events and the ERG was concerned with some of the assumptions related to HRQoL. In the base-case direct comparison, the incremental cost-effectiveness ratio (ICER) of topotecan plus cisplatin versus cisplatin monotherapy was 17,974 pounds per QALY in the main licensed population, 10,928 pounds per QALY in the cisplatin-naive population (including stage IVB patients) and 32,463 pounds per QALY in sustained cisplatin-free interval patients. In response to the point for clarification raised by the ERG, the manufacturer submitted a revised indirect comparison incorporating HRQoL and a longer time horizon. Where the hazard ratio derived from GOG-0169 was employed, paclitaxel plus cisplatin was dominated by topotecan plus cisplatin, but, where the hazard ratio from GOG-0204 was adopted, paclitaxel plus cisplatin was found to have an ICER of 13,260 pounds per QALY versus topotecan plus cisplatin. At present there is a paucity of evidence available on the clinical effects of topotecan plus cisplatin and the effects of palliative treatment in general for women with advanced and recurrent carcinoma of the cervix. Further trials, or the implementation of registries, are required to establish the efficacy and safety of topotecan plus cisplatin. The guidance issued by NICE on 28 October 2009 as a result of the STA states that topotecan in combination with cisplatin is recommended as a treatment option for women with recurrent or stage IVB cervical cancer, only if they have not previously received cisplatin. Women who have previously received cisplatin and are currently being treated with topotecan in combination with cisplatin for the treatment of cervical cancer should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

Breastfeeding promotion for infants in neonatal units: a systematic review and economic analysis.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of interventions that promote or inhibit breastfeeding or feeding with breastmilk for infants admitted to neonatal units, and to identify an agenda for future research. DATA SOURCES: Electronic databases were searched (including MEDLINE and MEDLINE In-Process Citations, EMBASE, CINAHL, Maternity and Infant Care, PsycINFO, British Nursing Index and Archive, Health Management Information Consortium, Cochrane Central Register of Controlled Trials, Science Citation Index, Pascal, Latin American and Caribbean Health Sciences, MetaRegister of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, Health Technology Assessment Database, National Research Register) from inception to February 2008. Advisors identified further published or unpublished material. REVIEW METHODS: All papers fulfilled eligibility criteria covering participants, interventions, study design and outcomes. Results from primary studies were assessed and summarised in a qualitative synthesis for each type of intervention and across types of intervention. To estimate long-term cost utility, a decision tree was developed to synthesise data on enhanced staff contact, breastmilk effectiveness, incidence of necrotising enterocolitis (NEC) and sepsis, resource use, survival and utilities. RESULTS: Forty-eight studies met the selection criteria for the effectiveness review, of which 65% (31/48) were RCTs, and 17% (8/48) were conducted in the UK. Seven were rated as good quality and 28 as moderate quality. No studies met the selection criteria for the health economics review. There is strong evidence that short periods of kangaroo skin-to-skin contact increased the duration of any breastfeeding for 1 month after discharge [risk ratio (RR) 4.76, 95% confidence interval (CI) 1.19 to 19.10] and for more than 6 weeks (RR 1.95, 95% CI 1.03 to 3.70) among clinically stable infants in industrialised settings. There is strong evidence for the effectiveness of peer support at home (in Manila) for mothers of term, low birthweight infants on any breastfeeding up to 24 weeks (RR 2.18, 95% CI 1.45 to 3.29) and exclusive breastfeeding from birth to 6 months (RR 65.94, 95% CI 4.12 to 1055.70), and for the effectiveness of peer support in hospital and at home for mothers of infants in Special Care Baby Units on providing any breastmilk at 12 weeks [odds ratio (OR) 2.81, 95% CI 1.11 to 7.14; p = 0.01]. There is more limited evidence for the effectiveness of skilled professional support in a US Neonatal Intensive Care Unit on infants receiving any breastmilk at discharge (OR 2.0, 95% CI 1.2 to 3.2, p = 0.004). Multidisciplinary staff training may increase knowledge and can increase initiation rates and duration of breastfeeding, although evidence is limited. Lack of staff training is an important barrier to implementation of effective interventions. Baby Friendly accreditation of the associated maternity hospital results in improvements in several breastfeeding-related outcomes for infants in neonatal units. Limited evidence suggests that cup feeding (versus bottle feeding) may increase breastfeeding at discharge and reduce the frequency of oxygen desaturation. Breastmilk expression using simultaneous pumping with an electric pump has advantages in the first 2 weeks. Pharmaceutical galactagogues have little benefit among mothers who have recently given birth. Our economic analysis found that additional skilled professional support in hospital was more effective and less costly (due to reduced neonatal illness) than normal staff contact. Additional support ranged from 0.009 quality-adjusted life-years (QALYs) to 0.251 QALYs more beneficial per infant and ranged from 66 pounds to 586 pounds cheaper per infant across the birthweight subpopulations. Donor milk would become cost-effective given improved mechanisms for its provision. CONCLUSIONS: Despite the limitations of the evidence base, kangaroo skin-to-skin contact, peer support, simultaneous breastmilk pumping, multidisciplinary staff training and the Baby Friendly accreditation of the associated maternity hospital have been shown to be effective, and skilled support from trained staff in hospital has been shown to be potentially cost-effective. All these point to future research priorities. Many of these interventions inter-relate: it is unlikely that specific clinical interventions will be effective if used alone. There is a need for national surveillance of feeding, health and cost outcomes for infants and mothers in neonatal units; to assist this goal, we propose consensus definitions of the initiation and duration of breastfeeding/breastmilk feeding with specific reference to infants admitted to neonatal units and their mothers.

Etanercept and efalizumab for the treatment of psoriasis: a systematic review.

OBJECTIVES: To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and efalizumab for the treatment of moderate to severe chronic plaque psoriasis. DATA SOURCES: Major electronic databases and several Internet resources were searched up to April 2004. REVIEW METHODS: Systematic reviews were undertaken of the efficacy, safety and economic reviews of etanercept and efalizumab. An existing systematic review of the efficacy and safety of other treatments was also updated. Economic models supplied by the manufacturers of etanercept and efalizumab were critiqued. An economic model was then developed of etanercept and efalizumab in the treatment of moderate to severe chronic plaque psoriasis. RESULTS: The review of the clinical evidence identified a total of 39 published and three unpublished studies: eight randomised controlled trials (RCTs) of the efficacy of etanercept (three trials) and efalizumab (five); 10 studies of the adverse effects of the interventions; and 24 RCTs of the efficacy of the other treatments for moderate to severe psoriasis. The trials of the efficacy of the interventions were all double-blind and placebo-controlled trials and generally of good quality, but three of the five efalizumab trials were poorly reported. A total of 1347 patients were included in the etanercept trials and 2963 in the efalizumab trials. Data on the efficacy of etanercept 25 mg twice a week for 12 weeks were available from three RCTs. On average, active treatment resulted in 62% of patients achieving a Psoriasis Area and Severity Index (PASI) 50, 33% achieving a PASI 75, 11% achieving a PASI 90 and 40% were assessed as clear or almost clear. These figures are not adjusted for changes relative to placebo. Improvement in quality of life as assessed by mean percentage change in Dermatology Life Quality Index (DLQI) was around 59% with etanercept 25 mg twice a week compared with 9% with placebo, and all mean differences that could be calculated were statistically significantly in favour of etanercept. Data on the efficacy of etanercept 50 mg twice a week for 12 weeks were available from two RCTs. Across the two trials, the proportion of patients achieving PASI 50, 75 and 90 was 76, 49 and 21%, respectively; the pooled relative risks were all statistically significantly in favour of etanercept. The findings for mean PASI after treatment, mean percentage change in PASI from baseline and mean percentage change in DLQI also demonstrated the efficacy of etanercept treatment. Evidence from one RCT indicates that the response to etanercept is maintained post-treatment, at least in the medium term, and data from uncontrolled follow-up phases reflect and extend these findings. Efalizumab at a dose of 1 mg/kg once a week subcutaneously was studied in five RCTs. Across these trials, 12 weeks of active treatment resulted in an average of 55% of patients achieving PASI 50, 27% PASI 75, 4.3% PASI 90 and 27% clear or minimal psoriasis status. These figures are not adjusted for changes relative to placebo. There is no evidence from RCTs that the response to efalizumab 1 mg/kg once a week is maintained when treatment continues beyond 12 weeks, and long-term follow-up data relate to a range of doses and are poorly reported and so cannot be used to draw even tentative conclusions regarding the long-term efficacy of efalizumab. Uncontrolled data from trial follow-up suggest that time to relapse may be around 60 days. No data indicating the existence or absence of any rebound in psoriasis after discontinuation of efalizumab were identified. There is no evidence relating to the efficacy of efalizumab upon retreatment. A mixed treatment comparison analysis found a higher response rate in terms of PASI 50, 75 and 90 with etanercept than with efalizumab. Injection site reactions appear to be the most common adverse effects of etanercept. Overall, etanercept appears to be well tolerated in short- and long-term use, although many of the long-term data are not from patients with psoriasis. Headache, chills and, to a lesser extent, nausea, myalgia, pain and fever are the common adverse events associated with efalizumab. Overall, withdrawal rates due to adverse events are low. Longer term data for efalizumab are not readily available for evaluation, but the adverse events data up to 3 years appear to reflect those over 12 weeks and to remain stable. Unfortunately, few data for serious infections and serious adverse events with efalizumab are available. For the primary analysis comparing etanercept, efalizumab and supportive care, the results of the York Model suggest that the biological therapies would only be cost-effective for all patients with moderate to severe psoriasis if the NHS were willing to pay over pound 60,000 per QALY gained. In patients with poor baseline quality of life (fourth quartile DLQI), efalizumab, etanercept 25 mg (intermittent), etanercept 25 mg (continuous) and etanercept 50 mg (intermittent) would be cost-effective as part of a treatment sequence if the NHS were willing to pay pound 45,000, pound 35,000, pound 45,000 and pound 65,000 per QALY gained, respectively. In patients who are also at high risk of inpatient hospitalisation (21 days per annum), these therapies would be cost-effective as part of a sequence as long as the NHS were willingness to pay pound 25,000, pound 20,000, pound 25,000 and pound 45,000 per QALY gained, respectively. As part of a secondary analysis including a wider range of systemic therapies as comparators, the York Model found that it would only be cost-effective to use etanercept and efalizumab in a sequence after methotrexate, ciclosporin and Fumaderm. CONCLUSIONS: Clinical trial data indicate that both etanercept and efalizumab are efficacious in patients who are eligible for systemic therapy, but the economic evaluation demonstrates that these biological therapies are likely to be cost-effective only in patients with poor baseline QoL and who are at risk of hospitalisation. Efficacy trials conducted in the specific population for which etanercept and efalizumab are licensed are required, as are long-term comparisons of etanercept and efalizumab with other treatments for moderate to severe psoriasis. Long-term efficacy trials and safety/tolerability data for patients treated with etanercept or efalizumab are required, as are trials on the response of specific subtypes of psoriasis to different drugs. Research on the rate of inpatient hospitalisation in patients with moderate to severe psoriasis is warranted, and the effect of treatment on this rate.

Evidence into practice: an information service for primary care professionals.

This paper describes the development of the Primary Care Information Service (PCIS) in South Humber Health Authority--a practical example of an information service which aims to make it easier for primary care practitioners to have access to information services and resources, both by electronic and more traditional means. Also, issues to consider when establishing a service for primary care professionals, including barriers to be overcome, are outlined, and an examination is made of how the service has been developed around principles of evidence-based medicine. Finally, the achievements to-date are considered.

Comparison of search strategies and quality of medical information of the Internet: a study relating to ankle sprain.

OBJECTIVES: to evaluate the quality of web sites on ankle sprain diagnosis and treatment and to assess the impact of Internet search expertise on quality of retrieved information. METHOD: two internet search strategies were conducted - one developed by an experienced information officer (expert's search) and the other based on the search terms used by orthopaedic medical staff (doctors' search). RESULTS: the expert's search revealed 32 web sites, of which nine were relevant, whereas the doctors' search revealed 61 web sites of which 27 were relevant. Of the relevant web sites in the expert's search, one complied with all quality criteria, whereas none of the web sites in the doctors' search complied with all criteria (11 vs. 0%, P=0.25). The web sites identified by expert's search had higher credibility (median scores 70 vs. 44, P=0.01) and accuracy of content (median scores 50 vs. 35, P=0.24). CONCLUSION: the quality of medical information on the internet is generally poor and information experts can capture higher quality web sites compared with doctors.