The effectiveness and safety of heat/cold therapy in adults with lymphoedema: systematic review.

PURPOSE: The aim of this review is to assess the efficacy and safety of using heat and cold therapy for adults with lymphoedema. METHODS: A multi-database search was undertaken. Only studies which included adults with lymphoedema who were treated with heat or cold therapy reporting any outcome were included. Screening, data extraction, and assessment of bias were undertaken by a single reviewer and verified by a second. Due to the substantial heterogeneity, a descriptive synthesis was undertaken. RESULTS: Eighteen studies were included. All nine studies which assessed the effects of heat-therapy on changes in limb circumference reported a point estimate indicating some reduction from baseline to end of study. Similarly, the five studies evaluating the use of heat-therapy on limb volume demonstrated a reduction in limb volume from baseline to end-of-study. Only four studies reported adverse events of which all were deemed to be minor. Only two studies explored the effects of cold therapy on lymphoedema. CONCLUSIONS: Tentative evidence suggests heat-therapy may have some benefit in treating lymphoedema with minimal side effects. However, further high-quality randomised controlled trials are required, with a particular focus on moderating factors and assessment of adverse events.Implications for rehabilitationThis review highlights the potential benefit that heat therapy may have on reducing limb circumference and volume for adults with lymphoedema.There was no evidence that controlled localised heat therapy was unsafe.The current evidence-base is at a point where no specific clinical recommendations can be made.The use of heat therapy should only be applied as part of a methodologically robust study to treat lymphoedema.

Reducing broad-spectrum antibiotic use in intensive care unit between first and second waves of COVID-19 did not adversely affect mortality.

BACKGROUND: The COVID-19 pandemic increased the use of broad-spectrum antibiotics due to diagnostic uncertainty, particularly in critical care. Multi-professional communication became more difficult, weakening stewardship activities. AIM: To determine changes in bacterial co-/secondary infections and antibiotics used in COVID-19 patients in critical care, and mortality rates, between the first and second waves. METHODS: Prospective audit comparing bacterial co-/secondary infections and their treatment during the first two waves of the pandemic in a single-centre teaching hospital intensive care unit. Data on demographics, daily antibiotic use, clinical outcomes, and culture results in patients diagnosed with COVID-19 infection were collected over 11 months. FINDINGS: From March 9th, 2020 to September 2nd, 2020 (Wave 1), there were 156 patients and between September 3rd, 2020 and February 1st, 2021 (Wave 2) there were 235 patients with COVID-19 infection admitted to intensive care. No significant difference was seen in mortality or positive blood culture rates between the two waves. The proportion of patients receiving antimicrobial therapy (93.0% vs 81.7%; P < 0.01) and the duration of meropenem use (median (interquartile range): 5 (2-7) vs 3 (2-5) days; P = 0.01) was lower in Wave 2. However, the number of patients with respiratory isolates of Pseudomonas aeruginosa (4/156 vs 21/235; P < 0.01) and bacteraemia from a respiratory source (3/156 vs 20/235; P < 0.01) increased in Wave 2, associated with an outbreak of infection. There was no significant difference between waves with respect to isolation of other pathogens. CONCLUSION: Reduced broad-spectrum antimicrobial use in the second wave of COVID-19 compared with the first wave was not associated with significant change in mortality.

The effect of ageing on skeletal muscle as assessed by quantitative MR imaging: an association with frailty and muscle strength.

BACKGROUND: Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. AIMS: To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. METHODS: 18 'young' (18-30 years), 18 'middle-aged' (31-68 years) and 18 'older' (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. RESULTS: Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. DISCUSSION: Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. CONCLUSIONS: Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle.

Moving Towards Common Data Elements and Core Outcome Measures in Frailty Research.

With aging populations around the world, frailty is becoming more prevalent increasing the need for health systems and social systems to deliver optimal evidence based care. However, in spite of the growing number of frailty publications, high-quality evidence for decision making is often lacking. Inadequate descriptions of the populations enrolled including frailty severity and frailty conceptualization, lack of use of validated frailty assessment tools, utilization of different frailty instruments between studies, and variation in reported outcomes impairs the ability to interpret, generalize and implement the research findings. The utilization of common data elements (CDEs) and core outcome measures (COMs) in clinical trials is increasingly being adopted to address such concerns. To catalyze the development and use of CDEs and COMs for future frailty studies, the Canadian Frailty Network (www.cfn-nce.ca; CFN), a not-for-profit pan-Canadian nationally-funded research network, convened an international group of experts to examine the issue and plan the path forward. The meeting was structured to allow for an examination of current frailty evidence, ability to learn from other COMs and CDEs initiatives, discussions about specific considerations for frailty COMs and CDEs and finally the identification of the necessary steps for a COMs and CDEs consensus initiative going forward. It was agreed at the onset of the meeting that a statement based on the meeting would be published and herein we report the statement.

Reliability of frailty assessment in the critically ill: a multicentre prospective observational study.

Demand for critical care among older patients is increasing in many countries. Assessment of frailty may inform discussions and decision making, but acute illness and reliance on proxies for history-taking pose particular challenges in patients who are critically ill. Our aim was to investigate the inter-rater reliability of the Clinical Frailty Scale for assessing frailty in patients admitted to critical care. We conducted a prospective, multi-centre study comparing assessments of frailty by staff from medical, nursing and physiotherapy backgrounds. Each assessment was made independently by two assessors after review of clinical notes and interview with an individual who maintained close contact with the patient. Frailty was defined as a Clinical Frailty Scale rating > 4. We made 202 assessments in 101 patients (median (IQR [range]) age 69 (65-75 [60-80]) years, median (IQR [range]) Acute Physiology and Chronic Health Evaluation II score 19 (15-23 [7-33])). Fifty-two (51%) of the included patients were able to participate in the interview; 35 patients (35%) were considered frail. Linear weighted kappa was 0.74 (95%CI 0.67-0.80) indicating a good level of agreement between assessors. However, frailty rating differed by at least one category in 47 (47%) cases. Factors independently associated with higher frailty ratings were: female sex; higher Acute Physiology and Chronic Health Evaluation II score; higher category of pre-hospital dependence; and the assessor having a medical background. We identified a good level of agreement in frailty assessment using the Clinical Frailty Scale, supporting its use in clinical care, but identified factors independently associated with higher ratings which could indicate personal bias.

Assessment of frailty in the inpatient setting.

Frailty is a common condition which results in increased risk of adverse outcomes following hospital admission. This review looks at how to identify, assess and manage frail patients in the inpatient setting.

The prevalence and outcomes of frailty in older cancer patients: a systematic review.

BACKGROUND: Frailty is a state of vulnerability to poor resolution of homeostasis following a stressor event, such as chemotherapy or cancer surgery. Better knowledge of the epidemiology of frailty could help drive a global cancer care strategy for older people. The aim of this review was to establish the prevalence and outcomes of frailty and pre-frailty in older cancer patients. METHODS: Observational studies that reported data on the prevalence and/or outcomes of frailty in older cancer patients with any stage of solid or haematological malignancy were considered. We searched Medline, CINAHL, Cochrane Library, EMBASE, Web of Science, Allied and Complementary medicine, Psychinfo and ProQuest (1 January 1996 to 30 June 2013). The primary outcomes were prevalence of frailty, treatment-related side-effects, unplanned hospitalization and mortality. Risk of bias was assessed using the Newcastle-Ottawa checklist. RESULTS: Data from 20 studies evaluating 2916 participants are included. The median reported prevalence of frailty and pre-frailty was 42% (range 6%-86%) and 43% (range 13%-79%), respectively. A median of 32% (range 11%-78%) of patients were classified as fit. Frailty was independently associated with increased all-cause mortality [adjusted 5-year hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.36-2.57]. There was evidence of increased risk of postoperative mortality for both frailty (adjusted 30-day HR 2.67, 95% CI 1.08-6.62) and pre-frailty (adjusted HR 2.33, 95% CI 1.20-4.52). Treatment complications were more frequent in those with frailty, including intolerance to cancer treatment (adjusted odds ratio 4.86, 95% CI 2.19-10.78) and postoperative complications (adjusted 30-day HR 3.19, 95% CI 1.68-6.04). CONCLUSIONS: More than half of older cancer patients have pre-frailty or frailty and these patients are at increased risk of chemotherapy intolerance, postoperative complications and mortality. The findings of this review support routine assessment of frailty in older cancer patients to guide treatment decisions, and the development of multidisciplinary geriatric oncology services.

Using process data to understand outcomes in sexual health promotion: an example from a review of school-based programmes to prevent sexually transmitted infections.

This article discusses how process indicators can complement outcomes as part of a comprehensive explanatory evaluation framework, using the example of skills-based behavioural interventions to prevent sexually transmitted infections and promote sexual health among young people in schools. A systematic review was conducted, yielding 12 eligible outcome evaluations, 9 of which included a process evaluation. There were few statistically significant effects in terms of changes in sexual behaviour outcomes, but statistically significant effects were more common for knowledge and self-efficacy. Synthesis of the findings of the process evaluations identified a range of factors that might explain outcomes, and these were organized into two overarching categories: the implementation of interventions, and student engagement and intervention acceptability. Factors which supported implementation and engagement and acceptability included good quality teacher training, involvement and motivation of key school stakeholders and relevance and appeal to young people. Factors which had a negative impact included teachers' failure to comprehend the theoretical basis for behaviour change, school logistical problems and omission of topics that young people considered important. It is recommended that process indicators such as these be assessed in future evaluations of school-based sexual health behavioural interventions, as part of a logic model.

Are educational interventions to prevent catheter-related bloodstream infections in intensive care unit cost-effective?

BACKGROUND: There is increasing interest in evidence-based educational interventions in central venous catheter care. It is unclear how effective these are at reducing the risk of bloodstream infections from the use of intravascular catheters (catheter-BSIs) and the associated costs and health benefits. AIM: To estimate the additional costs and health benefits from introducing such interventions and the costs associated with catheter-BSIs. METHODS: A comprehensive epidemiological and economic review was performed to develop the parameters for an economic model to assess the cost-effectiveness of introducing an educational intervention compared with clinical practice without the intervention. The model follows the clinical pathway of cohorts of patients from their admission to an intensive care unit (ICU), where some may acquire catheter-BSI, and estimates the associated costs, mortality and life expectancy. FINDINGS: The additional cost per catheter-BSI episode was £3940. The results of this model demonstrate that introducing an additional educational intervention to prevent catheter-BSI improved patient life expectancy and reduced overall costs. CONCLUSION: Introducing evidence-based education is likely to reduce the incidence of catheter-BSI and the model results suggest that the cost of introducing the interventions will be outweighed by savings related to reduced ICU bed occupancy costs.

Dasatinib, high-dose imatinib and nilotinib for the treatment of imatinib-resistant chronic myeloid leukaemia: a systematic review and economic evaluation.

BACKGROUND: The present report was commissioned as a supplement to an existing technology assessment report produced by the Peninsula Technology Assessment Group (PenTAG), which evaluated the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in patients who are either resistant or intolerant to standard-dose imatinib. OBJECTIVES: This report evaluates the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and high-dose imatinib within their licensed indications for the treatment of people with chronic myeloid leukaemia (CML) who are resistant to standard-dose imatinib. DATA SOURCES: Bibliographic databases were searched from inception to January 2011, including The Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences were searched, and experts were contacted to identify additional published and unpublished references. REVIEW METHODS: This report includes systematic reviews of clinical effectiveness and cost-effectiveness studies, an independent appraisal of information submitted by drug manufacturers to the National Institute for Health and Clinical Excellence (NICE), an independent appraisal of the PenTAG economic evaluation, and new economic analyses adapting the PenTAG economic model. Standard systematic procedures involving two reviewers to maintain impartiality and transparency, and to minimise bias, were conducted. RESULTS: Eleven studies met the inclusion criteria. Four of these studies included new data published since the PenTAG report; all of these were in chronic-phase CML. No relevant studies on the clinical effectiveness of nilotinib were found. The clinical effectiveness studies on dasatinib [one arm of a randomised controlled trial (RCT)] and high-dose imatinib (one arm of a RCT and three single-arm cohort studies) had major methodological limitations. These limitations precluded a comparison of the different arms within the RCT. Data from the studies are summarised in this report, but caution in interpretation is required. One economic evaluation was identified that compared dasatinib with high-dose imatinib in patients with chronic-phase CML who were CML resistant to standard-dose imatinib. Two industry submissions and the PenTAG economic evaluation were critiqued and differences in the assumptions and results were identified. The PenTAG economic model was adapted and new analyses conducted for the interventions dasatinib, nilotinib and high-dose imatinib and the comparators interferon alfa, standard-dose imatinib, stem cell transplantation and hydroxycarbamide. The results suggest that the three interventions, dasatinib, nilotinib and high-dose imatinib, have similar costs and cost-effectiveness compared with hydroxycarbamide, with a cost-effectiveness of around £30,000 per quality-adjusted life-year gained. However, it is not possible to derive firm conclusions about the relative cost-effectiveness of the three interventions owing to great uncertainty around data inputs. Uncertainty was explored using deterministic sensitivity analyses, threshold analyses and probabilistic sensitivity analyses. LIMITATIONS: The paucity of good-quality evidence should be considered when interpreting this report. CONCLUSIONS: This review has identified very limited new information on clinical effectiveness of the interventions over that already shown in the PenTAG report. Limitations in the data exist; however, the results of single-arm studies suggest that the interventions can lead to improvements in haematological and cytogenetic responses in people with imatinib-resistant CML. The economic analyses do not highlight any one of the interventions as being the most cost-effective; however, the analysis results are highly uncertain owing to lack of agreement on appropriate assumptions. Recommendations for future research made by PenTAG, for a good-quality RCT comparing the three treatments remain.

The effectiveness of interventions to treat severe acute malnutrition in young children: a systematic review.

BACKGROUND: Severe acute malnutrition (SAM) arises as a consequence of a sudden period of food shortage and is associated with loss of a person's body fat and wasting of their skeletal muscle. Many of those affected are already undernourished and are often susceptible to disease. Infants and young children are the most vulnerable as they require extra nutrition for growth and development, have comparatively limited energy reserves and depend on others. Undernutrition can have drastic and wide-ranging consequences for the child's development and survival in the short and long term. Despite efforts made to treat SAM through different interventions and programmes, it continues to cause unacceptably high levels of mortality and morbidity. Uncertainty remains as to the most effective methods to treat severe acute malnutrition in young children. OBJECTIVES: To evaluate the effectiveness of interventions to treat infants and children aged < 5 years who have SAM. DATA SOURCES: Eight databases (MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, CAB Abstracts Ovid, Bioline, Centre for Reviews and Dissemination, EconLit EBSCO and The Cochrane Library) were searched to 2010. Bibliographies of included articles and grey literature sources were also searched. The project expert advisory group was asked to identify additional published and unpublished references. REVIEW METHODS: Prior to the systematic review, a Delphi process involving international experts prioritised the research questions. Searches were conducted and two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full texts of retrieved papers by one reviewer and checked independently by a second. Included studies were mapped to the research questions. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Differences in opinion were resolved through discussion at each stage. Studies were synthesised through a narrative review with tabulation of the results. RESULTS: A total of 8954 records were screened, 224 full-text articles were retrieved, and 74 articles (describing 68 studies) met the inclusion criteria and were mapped. No evidence focused on treatment of children with SAM who were human immunodeficiency virus sero-positive, and no good-quality or adequately reported studies assessed treatments for SAM among infants < 6 months old. One randomised controlled trial investigated fluid resuscitation solutions for shock, with none adequately treating shock. Children with acute diarrhoea benefited from the use of hypo-osmolar oral rehydration solution (H-ORS) compared with the standard World Health Organization-oral rehydration solution (WHO-ORS). WHO-ORS was not significantly different from rehydration solution for malnutrition (ReSoMal), but the safety of ReSoMal was uncertain. A rice-based ORS was more beneficial than glucose-based ORSs, and provision of zinc plus a WHO-ORS had a favourable impact on diarrhoea and need for ORS. Comparisons of different diets in children with persistent diarrhoea produced conflicting findings. For treating infection, comparison of amoxicillin with ceftriaxone during inpatient therapy, and routine provision of antibiotics for 7 days versus no antibiotics during outpatient therapy of uncomplicated SAM, found that neither had a significant effect on recovery at the end of follow-up. No evidence mapped to the next three questions on factors that affect sustainability of programmes, long-term survival and readmission rates, the clinical effectiveness of management strategies for treating children with comorbidities such as tuberculosis and Helicobacter pylori infection and the factors that limit the full implementation of treatment programmes. Comparison of treatment for SAM in different settings showed that children receiving inpatient care appear to do as well as those in ambulatory or home settings on anthropometric measures and response time to treatment. Longer-term follow-up showed limited differences between the different settings. The majority of evidence on methods for correcting micronutrient deficiencies considered zinc supplements; however, trials were heterogeneous and a firm conclusion about zinc was not reached. There was limited evidence on either supplementary potassium or nicotinic acid (each produced some benefits), and nucleotides (not associated with benefits). Evidence was identified for four of the five remaining questions, but not assessed because of resource limitation. LIMITATIONS: The systematic review focused on key questions prioritised through a Delphi study and, as a consequence, did not encompass all elements in the management of SAM. In focusing on evidence from controlled studies with the most rigorous designs that were published in the English language, the systematic review may have excluded other forms of evidence. The systematic review identified several limitations in the evidence base for assessing the effectiveness of interventions for treating young children with severe acute malnutrition, including a lack of studies assessing the different interventions; limited details of study methods used; short follow-up post intervention or discharge; and heterogeneity in participants, interventions, settings, and outcome measures affecting generalisability. CONCLUSIONS: For many of the most highly ranked questions evidence was lacking or inconclusive. More research is needed on a range of topic areas concerning the treatment of infants and children with SAM. Further research is required on most aspects of the management of SAM in children < 5 years, including intravenous resuscitation regimens for shock, management of subgroups (e.g. infants < 6 months old, infants and children with SAM who are human immunodeficiency virus sero-positive) and on the use of antibiotics.

The clinical effectiveness and cost-effectiveness of bortezomib and thalidomide in combination regimens with an alkylating agent and a corticosteroid for the first-line treatment of multiple myeloma: a systematic review and economic evaluation.

BACKGROUND: Multiple myeloma (MM) is the second most common haematological cancer in the UK. MM is not curable but can be treated with a combination of supportive measures and chemotherapy that aim to extend the duration and quality of survival. The majority of patients are not able to withstand intensive treatment, such as high-dose chemotherapy with autologous stem cell transplantation (SCT), and so they are offered single-agent or combination chemotherapy. Combination therapies typically include chemotherapy with an alkylating agent and a corticosteroid. More recently, combination therapies have incorporated drugs such as thalidomide (Thalidomide Celgene®, Celgene) and bortezomib (Velcade®, Janssen-Cilag). OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of bortezomib or thalidomide in combination chemotherapy regimens with an alkylating agent and a corticosteroid for the first-line treatment of MM. DATA SOURCES: Electronic bibliographic databases, including MEDLINE, EMBASE and The Cochrane Library, were searched from 1999 to 2009 for English-language articles. Bibliographies of articles, grey literature sources and manufacturers' submissions were also searched. Experts in the field were asked to identify additional published and unpublished references. REVIEW METHODS: Titles and abstracts were screened for eligibility by two reviewers independently. The inclusion criteria specified in the protocol were applied to the full text of retrieved papers by one reviewer and checked independently by a second reviewer. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Differences in opinion were resolved through discussion at each stage. A cost-utility decision-analytic model was used to compare the cost-effectiveness estimates of bortezomib in combination with melphalan and prednisolone/prednisone (VMP), thalidomide in combination with cyclophosphamide and attenuated dexamethasone (CTDa), and thalidomide in combination with melphalan and prednisolone/prednisone (MPT) versus melphalan and prednisolone/prednisone (MP). RESULTS: A total of 1436 records were screened and 40 references were retrieved for the systematic review of clinical effectiveness. Five randomised controlled trials (RCTs) met the inclusion criteria for the review: one RCT evaluated VMP, three evaluated MPT and one evaluated CTDa. The comparator in all of the included trials was MP. The review found that VMP and MPT can both be considered more clinically effective than MP for the first-line treatment of MM in people for whom high-dose therapy and SCT would not be appropriate. CTDa was more effective than MP in terms of complete response but data on survival outcomes did not meet the inclusion criteria. Cost-effectiveness analysis indicated that MPT has a greater probability of being cost-effective than either VMP or CTDa. LIMITATIONS: For most RCTs, details needed to judge study quality were incompletely reported. All studies stated that the analyses followed intention-to-treat principles but none adequately reported data censoring. Only one RCT contributed data on VMP and the published peer-reviewed follow-up data were immature. For MPT, overall survival data from two trials were eligible for inclusion but the doses of thalidomide differed between the trials and the treatment period was not reflective of current UK practice so the generalisability of the findings was uncertain. Two RCTs had a maintenance phase with thalidomide that did not meet the inclusion criteria so some of these results were not eligible for the review. Limited evidence on health-related quality of life (HRQoL) was provided by the single trial of VMP versus MP. CONCLUSIONS: Service provision is unlikely to change greatly. As uncertainties remain, further research is needed regarding the use of bortezomib- and thalidomide-containing combination regimens. Head-to-head trials of bortezomib- and thalidomide-containing combination regimes are required, including assessments of patient HRQoL in response to treatment. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Bone-anchored hearing aids for people with bilateral hearing impairment: a systematic review.

BACKGROUND: Bone-anchored hearing aids (BAHAs) are indicated for people with conductive or mixed hearing loss who can benefit from amplification of sound. In resource limited health care systems, it is important that evidence regarding the benefit of BAHAs is critically appraised to aid decision-making. OBJECTIVE OF REVIEW: To assess the clinical effectiveness of BAHAs for people with bilateral hearing impairment. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: Nineteen electronic resources were searched from inception to November 2009. Additional studies were sought from reference lists, clinical experts and BAHA manufacturers. EVALUATION METHOD: Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment of full papers were undertaken by one reviewer and checked by a second. Studies were synthesised through narrative review with tabulation of results. RESULTS: Twelve studies were included. Studies suggested audiological benefits of BAHAs when compared with bone-conduction hearing aids or no aiding. A mixed pattern of results was seen when BAHAs were compared to air-conduction hearing aids. Improvements in quality of life with BAHAs were found by a hearing-specific instrument but not generic quality of life measures. Issues such as improvement of discharging ears and length of time the aid can be worn were not adequately addressed by the studies. Studies demonstrated some benefits of bilateral BAHAs. Adverse events data were limited. The quality of the studies was low. CONCLUSIONS: The available evidence is weak. As such, caution is indicated in the interpretation of presently available data. However, based on the available evidence, BAHAs appear to be a reasonable treatment option for people with bilateral conductive or mixed hearing loss. Further research into the benefits of BAHAs, including quality of life, is required to reduce the uncertainty.

Bone-anchored hearing aids (BAHAs) for people who are bilaterally deaf: a systematic review and economic evaluation.

BACKGROUND: A bone-anchored hearing aid (BAHA) consists of a permanent titanium fixture, which is surgically implanted into the skull bone behind the ear, and a small detachable sound processor that clips onto the fixture. BAHAs are suitable for people with conductive or mixed hearing loss who cannot benefit fully from conventional hearing aids. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of BAHAs for people who are bilaterally deaf. DATA SOURCES: Nineteen electronic resources, including MEDLINE, EMBASE and The Cochrane Library (inception to November 2009). Additional studies were sought from reference lists and clinical experts. REVIEW METHODS: Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Prospective studies of adults or children with bilateral hearing loss were eligible. Comparisons were BAHAs versus conventional hearing aids [air conduction hearing aid (ACHA) or bone conduction hearing aid (BCHA)], unaided hearing and ear surgery; and unilateral versus bilateral BAHAs. Outcomes included hearing measures, validated measures of quality of life (QoL), adverse events and measures of cost-effectiveness. For the review of cost-effectiveness, full economic evaluations were eligible. RESULTS: Twelve studies were included (seven cohort pre-post studies and five cross-sectional 'audiological comparison' studies). No prospective studies comparing BAHAs with ear surgery were identified. Overall quality was rated as weak for all included studies and meta-analysis was not possible due to differences in outcome measures and patient populations. There appeared to be some audiological benefits of BAHAs compared with BCHAs and improvements in speech understanding in noise compared with ACHAs; however, ACHAs may produce better audiological results for other outcomes. The limited evidence reduces certainty. Hearing is improved with BAHAs compared with unaided hearing. Improvements in QoL with BAHAs were identified by a hearing-specific instrument but not generic QoL measures. Studies comparing unilateral with bilateral BAHAs suggested benefits of bilateral BAHAs in many, but not all, situations. Prospective case series reported between 6.1% and 19.4% loss of implants. Most participants experienced no or minor skin reactions. A decision analytic model was developed. Costs and benefits of unilateral BAHAs were estimated over a 10-year time horizon, applying discount rates of 3.5%. The incremental cost per user receiving BAHA, compared with BCHA, was £ 16,409 for children and £ 13,449 for adults. In an exploratory analysis the incremental cost per quality-adjusted life-year (QALY) gained was between £ 55,642 and £ 119,367 for children and between £ 46,628 and £ 100,029 for adults for BAHAs compared with BCHA, depending on the assumed QoL gain and proportion of each modelled cohort using their hearing aid for ≥ 8 or more hours per day. Deterministic sensitivity analysis suggested that the results were highly sensitive to the assumed proportion of people using BCHA for ≥ 8 hours per day, with very high incremental cost-effectiveness ratio values (£ 500,000-1,200,000 per QALY gained) associated with a high proportion of people using BCHA. More acceptable values (£ 15,000-37,000 per QALY gained) were associated with a low proportion of people using BCHA for ≥ 8 hours per day (compared with BAHA). LIMITATIONS: The economic evaluation presented in this report is severely limited by a lack of robust evidence on the outcome of hearing aid provision. This has lead to a more restricted analysis than was originally anticipated (limited to a comparison of BAHA and BCHA). In the absence of useable QoL data, the cost-effectiveness analysis is based on potential utility gains from hearing, that been inferred using a QoL instrument rather than measures reported by hearing aid users themselves. As a result the analysis is regarded as exploratory and the reported results should be interpreted with caution. CONCLUSIONS: Exploratory cost-effectiveness analysis suggests that BAHAs are unlikely to be a cost-effective option where the benefits (in terms of hearing gain and probability of using of alternative aids) are similar for BAHAs and their comparators. The greater the benefit from aided hearing and the greater the difference in the proportion of people using the hearing aid for ≥ 8 hours per day, the more likely BAHAs are to be a cost-effective option. The inclusion of other dimensions of QoL may also increase the likelihood of BAHAs being a cost-effective option. A national audit of BAHAs is needed to provide clarity on the many areas of uncertainty surrounding BAHAs. Further research into the non-audiological benefits of BAHAs, including QoL, is required.

The clinical effectiveness and cost-effectiveness of long-term weight management schemes for adults: a systematic review.

OBJECTIVE: To assess the long-term clinical effectiveness and cost-effectiveness of multicomponent weight management schemes for adults in terms of weight loss and maintenance of weight loss. DATA SOURCES: Bibliographic databases were searched from inception to December 2009, including the Cochrane Library, MEDLINE (Ovid), EMBASE (Ovid), and MEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were screened, key conferences and symposia were searched and experts were contacted to identify additional published and unpublished references. REVIEW METHODS: For the clinical effectiveness review, two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers by one reviewer and checked by a second reviewer using a pre-piloted inclusion flow chart. The studies were long-term randomised controlled trials (RCTs) of adult participants who were classified by body mass index as overweight or obese. Interventions were multicomponent weight management programmes (including diet, physical activity and behaviour change strategies) that assessed weight measures. Programmes that involved the use of over-the-counter medicines licensed in the UK were also eligible. For the cost-effectiveness review two reviewers independently screened studies for inclusion. Cost-effectiveness, cost-utility, cost-benefit or cost-consequence analyses were eligible. Data were extracted using a standardised and pre-piloted data extraction form. The quality of included studies was assessed using standard criteria. Studies were synthesised through a narrative review with full tabulation of results. RESULTS: A total of 3358 references were identified, of which 12 were included in the clinical effectiveness review. Five RCTs compared multicomponent interventions with non-active comparator groups. In general, weight loss appeared to be greater in the intervention groups than in the comparator groups. Two RCTs compared multicomponent interventions that focused on the diet component. In these studies there were no statistically significant differences in weight loss between interventions. Four RCTs compared multicomponent interventions that focused on the physical activity component. There was little consistency in the pattern of results seen, in part owing to the differences in the interventions. In one RCT the intervention focused on the goal-setting interval and it appeared that weight loss was greatest in those given daily goals compared with weekly goals. Overall, where measured, it appeared that most groups began to regain weight at further follow-up. Of the 419 studies identified in the cost-effectiveness searches, none met the full inclusion criteria. Two economic evaluations are described in our review; however, caution is required in their interpretation, as they did not meet all inclusion criteria. Lifetime chronic disease models were used in these studies and the models included the costs and benefits of avoiding chronic illness. Both studies found the interventions to be cost-effective, with estimates varying between -£473 and £7200 (US$12,640) per quality-adjusted life-year gained; methodological omissions from these studies were apparent and caution is therefore required in the interpretation of these results. CONCLUSIONS: Long-term multicomponent weight management interventions were generally shown to promote weight loss in overweight or obese adults. Weight changes were small however and weight regain was common. There were few similarities between the included studies; consequently an overall interpretation of the results was difficult to make. There is some evidence that weight management interventions are likely to be cost-effective, although caution is required as there were some limitations in the two cost-evaluation studies described. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The safety and effectiveness of different methods of earwax removal: a systematic review and economic evaluation.

BACKGROUND: Build-up of earwax is a common reason for attendance in primary care. Current practice for earwax removal generally involves the use of a softening agent, followed by irrigation of the ear if required. However, the safety and benefits of the different methods of removal are not known for certain. OBJECTIVES: To conduct evidence synthesis of the clinical effectiveness and cost-effectiveness of the interventions currently available for softening and/or removing earwax and any adverse events (AEs) associated with the interventions. DATA SOURCES: Eleven electronic resources were searched from inception to November 2008, including: The Cochrane Library; MEDLINE (OVID), PREMEDLINE In-Process & Other Non-Indexed Citations (OVID), EMBASE (OVID); and CINAHL. METHODS: Two reviewers screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text or retrieved papers and data were extracted by two reviewers using data extraction forms developed a priori. Any differences were resolved by discussion or by a third reviewer. Study criteria included: interventions - all methods of earwax removal available and combinations of these methods; participants - adults/children presenting requiring earwax removal; outcomes - measures of hearing, adequacy of clearance of wax, quality of life, time to recurrence or further treatment, AEs and measures of cost-effectiveness; design - randomised controlled trials (RCTs) and controlled clinical trials (CCTs) for clinical effectiveness, cohort studies for AEs and cost-effectiveness, and costing studies for cost-effectiveness. For the economic evaluation, a deterministic decision tree model was developed to evaluate three options: (1) the use of softeners followed by irrigation in primary care; (2) softeners followed by self-irrigation; and (3) a 'no treatment' option. Outcomes were assessed in terms of benefits to patients and costs incurred, with costs presented by exploratory cost-utility analysis. RESULTS: Twenty-six clinical trials conducted in primary care (14 studies), secondary care (8 studies) or other care settings (4 studies), met the inclusion criteria for the review - 22 RCTs and 4 CCTs. The range of interventions included 16 different softeners, with or without irrigation, and in various different comparisons. Participants, outcomes, timing of intervention, follow-up and methodological quality varied between studies. On measures of wax clearance Cerumol, sodium bicarbonate, olive oil and water are all more effective than no treatment; triethanolamine polypeptide (TP) is better than olive oil; wet irrigation is better than dry irrigation; sodium bicarbonate drops followed by irrigation by nurse is more effective than sodium bicarbonate drops followed by self-irrigation; softening with TP and self-irrigation is more effective than self-irrigation only; and endoscopic de-waxing is better than microscopic de-waxing. AEs appeared to be minor and of limited extent. Resuts of the exploratory economic model found that softeners followed by self-irrigation were more likely to be cost-effective [24,433 pounds per quality-adjusted life-year (QALY)] than softeners followed by irrigation at primary care (32,130 pounds per QALY) when compared with no treatment. Comparison of the two active treatments showed that the additional gain associated with softeners followed by irrigation at primary care over softeners followed by self-irrigation was at a cost of 340,000 pounds per QALY. When compared over a lifetime horizon to the 'no treatment' option, the ICERs for softeners followed by self-irrigation and of softeners followed by irrigation at primary care were 24,450 pounds per QALY and 32,136 pounds per QALY, respectively. LIMITATIONS: The systematic review found limited good-quality evidence of the safety, benefits and costs of the different strategies, making it difficult to differentiate between the various methods for removing earwax and rendering the economic evaluation as speculative. CONCLUSIONS: Although softeners are effective, which specific softeners are most effective remains uncertain. Evidence on the effectiveness of methods of irrigation or mechanical removal was equivocal. Further research is required to improve the evidence base, such as a RCT incorporating an economic evaluation to assess the different ways of providing the service, the effectiveness of the different methods of removal and the acceptability of the different approaches to patients and practitioners.

The clinical effectiveness and cost-effectiveness of topotecan for small cell lung cancer: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of topotecan as second-line treatment for small cell lung cancer (SCLC). DATA SOURCES: Bibliographic databases were searched from 1990 to February 2009, including the Cochrane library, MEDLINE (Ovid), EMBASE (Ovid), PREMEDLINE In-Process & Other Non-Indexed Citations. Bibliographies of related papers were assessed and experts were contacted to identify additional references and the manufacturer's submission to NICE was also searched. REVIEW METHODS: Two reviewers independently screened titles and abstracts for eligibility. Inclusion criteria were applied to the full text of retrieved papers using a standard form. For the clinical effectiveness review, the studies were randomised controlled trials (RCTs), which included adult participants with relapsed SCLC who responded to first-line treatment and for whom re-treatment with first-line therapy was inappropriate. The treatment was topotecan (oral or intravenous, i.v.) compared with one another, best supportive care (BSC) or other chemotherapy regimens. Outcomes included measures of response or disease progression and measures of survival. For the cost-effectiveness review studies were eligible for inclusion if they reported cost-effectiveness, cost-utility, cost-benefit or cost-consequence analyses. Data extraction and quality assessment of included studies was undertaken by one reviewer and checked by a second. Studies were synthesised through a narrative review with full tabulation of results. An independent economic model estimated the cost-effectiveness of topotecan (oral or i.v.) compared with BSC. The model used survival analysis methods to derive estimates of mean survival for patients treated with topotecan or receiving BSC alone. These were combined with quality of life (QoL) weights to derive estimates of mean quality-adjusted life expectancy for patients receiving BSC alone or topotecan plus BSC. Categories of costs included in the model included drug use, chemotherapy administration and on-treatment monitoring, management of adverse events, monitoring for disease progression and palliative care. RESULTS: A total of 434 references were identified of which five were included in the clinical effectiveness review. In these trials topotecan was compared with BSC, CAV [cyclophosphamide, Adriamycin (doxorubicin) and vincristine] or amrubicin, or oral topotecan was compared with i.v. topotecan. No economic evaluations were identified. There were no statistically significant differences between groups when i.v. topotecan was compared with either CAV or oral topotecan for overall response rate (ORR). Response rate was significantly better in participants receiving i.v. amrubicin than in those receiving a low dose of i.v. topotecan (38% versus 13%, respectively, p = 0.039). There was a statistically significant benefit in favour of oral topotecan compared with BSC (HR 0.61, 95% CI 0.43 to 0.87, p = 0.01). Drug acquisition costs for four cycles of treatment were estimated at 2550 pounds for oral topotecan and 5979 pounds for i.v. topotecan. Non-drug treatment costs accounted for an additional 1097 pounds for oral topotecan and 4289 pounds for i.v. topotecan. Total costs for the modelled time horizon of 5 years were 4854 pounds for BSC, 11,048 pounds for oral topotecan and between 16,914 pounds and 17,369 pounds for i.v. topotecan (depending on assumptions regarding time progression). Life expectancy was 0.4735, 0.7984 and 0.7784 years for BSC, oral topotecan and i.v. topotecan respectively. Total quality-adjusted life-years (QALYs) were 0.2247 and 0.4077, for BSC and oral topotecan respectively, resulting in an incremental cost-effectiveness ratio (ICER) of 33,851 pounds per QALY gained. Total QALYs for i.v. topotecan were between 0.3875 and 0.4157 (depending on assumptions regarding time progression) resulting in an ICER between 74,074 pounds and 65,507 pounds per QALY gained. CONCLUSIONS: Topotecan appeared to be better than BSC alone in terms of improved survival, and was as effective as CAV and less favourable than i.v. amrubicin in terms of response. Oral topotecan and i.v. topotecan were similar in efficacy. Topotecan offers additional benefit over BSC, but at increased cost. ICERs for i.v. topotecan, compared with BSC, were high and suggest that it is unlikely to be a cost-effective option. The ICER for oral topotecan is at the upper extreme of the range conventionally regarded as cost-effective from an NHS decision-making perspective. Further research into the QoL of patients with relapsed SCLC could identify the impacts of disease progression and treatment response.

The effectiveness and cost-effectiveness of behavioural interventions for the prevention of sexually transmitted infections in young people aged 13-19: a systematic review and economic evaluation.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of schools-based skills-building behavioural interventions to encourage young people to adopt and maintain safer sexual behaviour and to prevent them from acquiring sexually transmitted infections (STIs). DATA SOURCES: Electronic bibliographic databases (e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, CINAHL, PsycINFO, CCRCT, NHS EED and DARE) were searched for the period 1985 to March 2008. Bibliographies of systematic reviews and related papers were screened and experts contacted to identify additional published and unpublished references. REVIEW METHODS: A systematic review of effectiveness and economic evaluation of cost-effectiveness were carried out. A descriptive map of studies that met inclusion criteria was produced, and keywords were developed and systematically applied to these studies to identify a policy-relevant subset of studies for the systematic review. Outcome data for variables including sexual behaviour were extracted. An economic model was developed to compare the costs and consequences of the behavioural interventions. A Bernoulli statistical model was constructed to describe the probability of STI infection. RESULTS: There were few significant differences between the interventions and comparators in terms of changes in sexual behaviour outcomes, although there were some significant differences for knowledge and some measures of self-efficacy. The studies included in this review conducted relatively short follow-up assessments at a time when many young people were becoming sexually active. It is therefore possible that favourable behaviour change may have occurred, and become more cost-effective, with time, as sexual activity becomes more routine in young people's lives. The quality of the intervention provider influenced whether or not young people found the interventions to be acceptable and engaging; enthusiasm and considerable expertise were important for effective class management and delivery of skills-building activities, and a supportive school culture was also helpful. Recognition of young people's individual needs in relation to sexual health was another important factor. No conclusions could be drawn on the impact of the interventions on sexual health inequalities due to a lack of relevant data on socioeconomic status, gender and ethnicity. The results of the economic evaluation were considered to be illustrative, mainly due to the uncertainty of the effect of intervention on behavioural outcomes. The results were most sensitive to changes in parameter values for the intervention effect, the transmission probability of STIs and the number of sexual partners. The costs of teacher-led and peer-led behavioural interventions, based on the resources estimated from the relevant randomised controlled trials in our systematic review, were 4.30 pounds and 15 pounds per pupil, respectively. Teacher-led interventions were more cost-effective than peer-led interventions due to the less frequent need for training. The incremental cost-effectiveness of the teacher-led and peer-led interventions was 20,223 pounds and 80,782 pounds per quality-adjusted life-year gained, respectively. An analysis of individual parameters revealed that future research funding should focus on assessing the intervention effect for condom use from a school-based intervention. CONCLUSIONS: School-based behavioural interventions for the prevention of STIs in young people can bring about improvements in knowledge and increased self-efficacy, but the interventions did not significantly influence sexual risk-taking behaviour or infection rates. Future investigation should include long-term follow-up to assess the extent to which safer sexual behaviour is adopted and maintained into adulthood, and prospective cohort studies are needed to look at the parameters that describe the transmission of STIs between partners. Funding should focus on the effectiveness of the interventions on influencing behaviour.

Lapatinib for the treatment of HER2-overexpressing breast cancer.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of lapatinib for the treatment of advanced or metastatic HER2-overexpressing breast cancer based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The scope included women with advanced, metastatic or recurrent HER2-overexpressing breast cancer who have had previous therapy that includes trastuzumab. Outcomes were time to progression, progression-free survival, response rates, overall survival, health-related quality of life and adverse effects. The submission's evidence came from one randomised controlled trial (RCT) of reasonable methodological quality, although it was not powered to detect a statistically significant difference in mean overall survival. Median time to progression was longer in the lapatinib plus capecitabine arm than in the capecitabine monotherapy arm {27.1 [95% confidence interval (CI) 17.4 to 49.4] versus 18.6 [95% CI 9.1 to 36.9] weeks; hazard ratio 0.57 [95% CI 0.43 to 0.77; p = 0.00013]}. Median overall survival was very similar between the groups [67.7 (95% CI 58.9 to 91.6) versus 66.6 (95% CI 49.1 to 75.0) weeks; hazard ratio 0.78 (95% CI 0.55 to 1.12; p = 0.177)]. Median progression-free survival was statistically significantly longer in the lapatinib plus capecitabine group than in the capecitabine monotherapy group [27.1 (95% CI 24.1 to 36.9) versus 17.6 (95% CI 13.3 to 20.1) weeks; hazard ratio 0.55 (95% CI 0.41 to 0.74); p = 0.000033]. The manufacturer's economic model to estimate progression-free and overall survival for patients with HER2-positive advanced/metastatic breast cancer who had relapsed following treatment with an anthracycline, a taxane and trastuzumab was appropriate for the disease area. The base-case incremental cost-effectiveness ratios (ICERs) for lapatinib plus capecitabine compared with capecitabine monotherapy or vinorelbine monotherapy were higher than would conventionally be considered cost-effective. When compared with trastuzumab-containing regimes, lapatinib plus capecitabine dominated. In sensitivity analyses the ICER for lapatinib plus capecitabine compared with capecitabine monotherapy or vinorelbine monotherapy was robust to variation in assumptions. In all sensitivity analyses the ICERs remained higher than would conventionally be considered cost-effective. ICERs for trastuzumab-containing regimes were particularly sensitive to assumptions over the frequency of treatment, which had a large effect on the cost-effectiveness of lapatinib plus capecitabine. In conclusion, there was a general lack of evidence on the effectiveness of comparators included in the model and on key parameters such as dose adjustments and the model outputs need to be interpreted in the light of this uncertainty. At the time of writing, NICE were still considering the available evidence for this appraisal.