The economic burden of anxiety and depression on the working age population with diabetes in Spain.

Diabetes mellitus (DM) is a complex, chronic, multifactorial, and costly health problem representing 8% of total public health expenditures in Spain. The objective of this study was to analyse the prevalence and costs of Anxiety (AX) and Depression (DP) in the Spanish working population with DM. Data were obtained from the National Health Survey of Spain 2017. A multivariate analysis was conducted to predict the use of resources and absenteeism/presenteeism. Direct and indirect costs were calculated. The final population analysed contained 15,822 subjects (18-65 years old). DM prevalence was 4.8%, and AX-DP 10.6% (50.5% were men). Self-diagnosed health was rated as regular, poor or very poor in 89% of DM subjects with DP-AX. The average costs estimated were €24,643.41 for DM subjects with AX-DP and €20,059.53 for those with only DM. The total estimated 2017 economic impact of DM was 2.4% of Spanish gross domestic product (13% directly related to DP-AX). Indirect costs represented 72.7% of total DP-AX costs. Spanish society is paying a considerable price for the incidence of DP-AX levels with DM in the working population. This global challenge has important repercussions for individuals' quality of life, health systems, and countries' development and economic growth.

Empiric antibiotics for community-acquired pneumonia in adult patients: a systematic review and a network meta-analysis.

OBJECTIVE: The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) . METHOD: Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish. EXCLUSION CRITERIA: (1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format. DATA SOURCES: Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation. STATISTICAL ANALYSES: frequentist method performed with the 'netmeta' library, R package. RESULTS: 27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. For cure, two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). For mortality, three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate. CONCLUSION: For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692).

Indomethacin for intracranial hypertension secondary to severe traumatic brain injury in adults.

BACKGROUND: Among people who have suffered a traumatic brain injury, increased intracranial pressure continues to be a major cause of early death; it is estimated that about 11 people per 100 with traumatic brain injury die. Indomethacin (also known as indometacin) is a powerful cerebral vasoconstrictor that can reduce intracranial pressure and, ultimately, restore cerebral perfusion and oxygenation. Thus, indomethacin may improve the recovery of a person with traumatic brain injury. OBJECTIVES: To assess the effects of indomethacin for adults with severe traumatic brain injury. SEARCH METHODS: We ran the searches from inception to 23 August 2019. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8) in the Cochrane Library, Ovid MEDLINE, Ovid Embase, CINAHL Plus (EBSCO), four other databases, and clinical trials registries. We also screened reference lists and conference abstracts, and contacted experts in the field. SELECTION CRITERIA: Our search criteria included randomised controlled trials (RCTs) that compared indomethacin with any control in adults presenting with severe traumatic brain injury associated with elevated intracranial pressure, with no previous decompressive surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently decided on the selection of the studies. We followed standard Cochrane methods. MAIN RESULTS: We identified no eligible studies for this review, either completed or ongoing. AUTHORS' CONCLUSIONS: We found no studies, either completed or ongoing, that assessed the effects of indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. Thus, we cannot draw any conclusions about the effects of indomethacin on intracranial pressure, mortality rates, quality of life, disability or adverse effects. This absence of evidence should not be interpreted as evidence of no effect for indomethacin in controlling intracranial hypertension secondary to severe traumatic brain injury. It means that we have not identified eligible research for this review.

Efficacy and safety outcomes of recanalisation procedures in patients with acute symptomatic pulmonary embolism: systematic review and network meta-analysis.

BACKGROUND: We aimed to review the efficacy and safety of recanalisation procedures for the treatment of PE. METHODS: We searched PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through 31 July 2015 and included randomised clinical trials that compared the effect of a recanalisation procedure versus each other or anticoagulant therapy in patients diagnosed with PE. We used network meta-analysis and multivariate random-effects meta-regression to estimate pooled differences between each intervention and meta-regression to assess the association between trial characteristics and the reported effects of recanalisation procedures versus anticoagulation. RESULTS: For all-cause mortality, there were no significant differences in event rates between any of the recanalisation procedures and anticoagulant treatment (full-dose thrombolysis: OR 0.60; 95% CI0.36 to 1.01; low-dose thrombolysis: 0.47; 95% CI 0.14 to 1.59; and catheter-associated thrombolysis: 0.31; 95% CI 0.01 to 7.96). Full-dose thrombolysis increased the risk of major bleeding (2.00; 95% CI 1.06 to 3.78) compared with anticoagulation. Catheter-directed thrombolysis was associated with the lowest probability of dying (surface under the cumulative ranking curve (SUCRA), 0.67), followed by low-dose thrombolysis (SUCRA, 0.66) and full-dose thrombolysis (SUCRA, 0.55). Similarly, low-dose thrombolysis was associated with the lowest probability of major bleeding (SUCRA, 0.61), followed by catheter-directed thrombolysis (SUCRA, 0.54) and full-dose thrombolysis (SUCRA, 0.17). The results were similar in sensitivity analyses based on restricting only to studies in haemodynamically stable patients with PE. CONCLUSIONS: In the treatment of PE, recanalisation procedures do not seem to offer a clear advantage compared with standard anticoagulation. Low-dose thrombolysis was associated with the lowest probability of dying and bleeding. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015024670.

Cost-effectiveness Evaluation of the Inclusion of Dry Needling into an Exercise Program for Subacromial Pain Syndrome: Evidence from a Randomized Clinical Trial.

Objective: To evaluate the cost-effectiveness of the inclusion of trigger point-dry needling (TrP-DN) into an exercise program for the management of subacromial pain syndrome. Methods: Fifty patients with unilateral subacromial pain syndrome were randomized with concealed allocation to exercise alone or exercise plus TrP-DN. Both groups were asked to perform an exercise program targeting the rotator cuff musculature twice daily for five weeks. Patients allocated to the exercise plus TrP-DN group also received dry needling during the second and fourth sessions. Societal costs and health-related quality of life (estimated by EuroQol-5D-5L) over a one-year follow-up were used to generate incremental cost per quality-adjusted life-year (QALY) ratios for each intervention. Results: Intention-to-treat analysis was possible for 48 (96%) of the participants. Those in the exercise group made more visits to medical doctors and received a greater number of other treatments (P < 0.001). The major contributor to societal costs (77%) was the absenteeism paid labor in favor of the exercise plus TrP-DN group (P = 0.03). The combination of exercise plus TrP-DN was less costly (mean difference cost/patient = €517.34, P = 0.003) than exercise alone. Incremental QALYs showed greater benefit for exercise plus TrP-DN (difference = 2.87, 95% confidence interval = 2.85-2.89). Therefore, the inclusion of TrP-DN into an exercise program was more likely to be cost-effective than an exercise program alone, with 99.5% of the iterations falling in the dominant area. Conclusions: The inclusion of TrP-DN into an exercise program was more cost-effective for individuals with subacromial pain syndrome than exercise alone. From a cost-benefit perspective, the inclusion of TrP-DN into multimodal management of patients with subacromial pain syndrome should be considered.

The Role of Medical Societies and the Relevance of Clinical Perspective in the Evolving EU HTA Process: Insights Generated at the 2023 Fall Convention and Survey of the European Access Academy.

BACKGROUND: This work aimed to determine the role and action points for the involvement of medical societies in the European Health Technology Assessment (EU HTA) Methods: An online pre-convention survey was developed addressing four areas related to the EU HTA: (i) medical societies' role; (ii) role of clinical guidelines; (iii) interface with the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS); and (iv) approaching 'best-available evidence' (BAE). A descriptive analysis of questionnaire outcomes was conducted to inform the European Access Academy (EAA) Fall Convention 2023. Within the working groups (WGs), action points were identified and prioritised. RESULTS: A total of 57 experts from 15 countries responded to the survey. The WGs were attended by (i) 11, (ii) 10, (iii) 12, and (iv) 12 experts, respectively, representing a variety of national backgrounds and stakeholder profiles. The most relevant action points identified were as follows: (i) incorporation of clinical context into population, intervention, comparator, outcomes (PICO) schemes, (ii) timely provision of up-to-date therapeutic guidelines, (iii) ensuring the inclusion of MCBS insights into the EU HTA process, and (iv) considering randomized controlled trials (RCTs) as the gold standard and leveraging regulatory insights if development programs only include single-arm trials. CONCLUSIONS: The involvement of medical societies is a critical success factor for the EU HTA. The identified key action points foster the involvement of patient associations and medical societies.

Subjective assessment reported by patients shows differences between single-bundle and double-bundle anterior cruciate ligament reconstruction, systematic review and meta-analysis.

To determine the functional recovery, active reincorporation, and anteroposterior and rotational stability of patients undergoing anterior cruciate ligament (ACL) reconstruction using arthroscopy techniques with simple-bundle (SB) or double-bundle (DB). The following databases were searched: PubMed, Embase (Elsevier platform), the Cochrane Central Register of Controlled Trials (Wiley platform), Web of Science, and CINAHL. Level I and II studies involving anterior cruciate ligament arthroscopy were included in the search. Records were screened by title and abstract and assessed the risk of bias of selected studies. Meta-analyses using RevMan 5.3 software were conducted on the following outcomes: knee functionality, objective measurements of knee stability, rotational knee stability and knee anterior stability, sports reincorporation, and subjective assessments. Twenty-four studies of patients undergoing ACL reconstruction were included in the qualitative and quantitative synthesis (1707 patients) for Lysholm score, Subjective International Knee Documentation Committee (IKDC) score, Tegner score, KT-1000/2000, Lachman test, Objective IKDC score, and Pivot-Shift test. A return to pre-injury level showed a significant decrease in the Lysholm score (mean difference, - 0.99; 95% CI - 1.71 to - 0.40; P = 0.007) and Tegner score (mean difference, - 0.07; 95% CI, - 0.13 to - 0.01; P = 0.02) at DB reconstruction, similar to the knee functionality outcome of the subjective IKDC score (mean difference - 1.42; 95% CI - 2.46 to - 0.38; P = 0.007). There is no clear or significant difference in clinical stability and knee function or in sports incorporation with the true difference occurring in the subjective assessment.

The Role of Rehabilitative Ultrasound Imaging Technique in the Lumbopelvic Region as a Diagnosis and Treatment Tool in Physiotherapy: Systematic Review, Meta-Analysis and Meta-Regression.

Rehabilitative ultrasound imaging (RUSI) technique seems to be a valid and reliable tool for diagnosis and treatment in physiotherapy and has been widely studied in the lumbopelvic region the last three decades. The aims for this utility in clinical settings must be review through a systematic review, meta-analysis and meta-regression. A systematic review was designed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with PROSPERO registration and per review in all phases of the process using COVIDENCE, analysis of risk of bias and meta-analysis using REVMAN, and meta-regression calculation using STATA. Database screening provided 6544 references, out of which 321 reported narrative synthesis, and 21 reported quantitative synthesis, while only 7 of them provided comparable data to meta-analyze the variables pain and muscle thickness. In most cases, the forest plots showed considerable I2 heterogeneity indexes for multifidus muscle thickness (I2 = 95%), low back pain (I2 = 92%) and abdominal pain (I2 = 95%), not important for transversus abdominis muscle thickness (I2 = 22%), significant heterogenity (I2 = 69%) depending on the subgroup and not important internal oblique muscle thickness (I2 = 0%) and external oblique muscle thickness (I2 = 0%). Meta-regression did not provide significant data for the correlations between the variables analyzed and the intervention, age, and BMI (Body Mass Index). This review reveals that RUSI could contribute to a high reliability of the measurements in the lumbopelvic region with validity and reliability for the assessments, as well as showing promising results for diagnosis and intervention assessment in physiotherapy compared to the traditional model, allowing for future lines of research in this area.

Cost-effectiveness analysis of a surveillance program to prevent hip dislocation in children with cerebral palsy.

OBJECTIVE: In this study we conducted an economic evaluation of a surveillance programme to prevent hip dislocation in children with cerebral palsy. METHOD: We developed a model that compared costs and health outcomes of children with cerebral palsy with and without a surveillance programme. Information from a number of sources was combined into a decision analytical model, primarily based on data from a comparative study with a 20-year follow-up. Effectiveness was measured using Quality-Adjusted Life Years (QALYs). The analysis took the perspective of the Spanish National Health Service. We undertook extensive sensitivity analyses including a probabilistic sensitivity analysis. RESULTS: The surveillance programme led to higher QALYs and higher health care costs, with an estimated incremental cost per QALY gained of 12,282€. The results were robust to model assumptions. The probability that the programme was cost-effective was estimated to be over 80% at the threshold of 25.000€/QALY recommended in Spain. CONCLUSION: This study indicates that surveillance programmes to prevent hip dislocation in children with cerebral palsy are likely to be cost-effective.

Endoscopist-directed propofol is more efficient than anesthesiologist-administered propofol in patients at low-intermediate anesthetic risk.

OBJECTIVE: Endoscopist-directed propofol (EDP) sedation is becoming more popular, with a reported safety and efficacy similar to anesthesiologist-administered propofol (AAP). The aim of this study is to compare the efficiency of EDP and AAP in patients of low-intermediate anesthetic risk. METHODS: A prospective cost-effectiveness comparison study was conducted. The costs of the endoscopic procedures in the EDP and AAP group were calculated using the full cost methodology after breaking down the endoscopic activity into relative value units to allocate costs in an equitable way. To determine the effectiveness, adverse events related to endoscopic sedation and the number of incomplete procedures were registered for the EDP group and compared with those published by anesthesiologists for AAP. RESULTS: A total of 1165 and 18 919 endoscopic procedures were, respectively, included in the EDP and AAP groups. The average costs of EDP vs. AAP for gastroscopy, colonoscopy and endoscopic ultrasound were &OV0556; 182.81 vs. &OV0556; 332.93, &OV0556; 297.07 vs. &OV0556; 459.76, and &OV0556; 319.92 vs. &OV0556; 485.12, respectively. No significant differences were detected regarding the rate of overall adverse events (4.43 vs. 4.46%) or serious adverse events (0 vs. 0.17%); the rate of arterial hypotension was significantly lower in the EDP group: 0.34 vs. 1.78% [odds ratio (OR), 0.19; 95% confidence interval (CI), 0.08-0.46] and the desaturation rate was significantly lower in the AAP group: 3.26 vs. 1.29% (OR, 2.58; 95% CI, 1.85-3.60). No significant differences were found in terms of incomplete examinations (0.17 vs. 0.14%). CONCLUSION: In patients with low-intermediate anesthetic risk referred for an endoscopic examination, EDP appears to be more efficient than AAP.

Effectiveness of immunosuppression minimisation, conversion or withdrawal strategies in paediatric solid organ and haematopoietic stem cell transplantation: a protocol of a systematic review and meta-analysis.

INTRODUCTION: Paediatric transplantation is the only curative therapeutic procedure for several end-stage rare diseases affecting different organs and body systems, causing altogether great impact in European children's health and quality of life. Transplanted children shift their primary disease to a chronic condition of immunosuppression to avoid rejection. Longer life expectancy in children poses a greater risk of prolonged and severe side effects related to long-term immunosuppressive (IS) disabilities and secondary cancer susceptibility. The goal remains to find the best combination of IS agents that optimises allograft survival by preventing acute rejection while limiting drug toxicities. This systematic review will aim to determine the optimal IS strategy within the so-called minimisation, conversion or withdrawal strategies. METHODS AND ANALYSIS: We will search the following databases with no language restrictions: Cochrane Central Register of Controlled Trials in the Cochrane Library, OvidSP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; OvidSP Embase Classic+Embase; Ebsco CINAHL Plus, complete database; WHO International Clinical Trials Registry Platform search portal. We will include controlled and uncontrolled clinical trials along with any prospective or retrospective study that includes a universal cohort (all participants from a centre/region/city over a certain period). Cases series and cross-sectional studies are excluded. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. The outcomes included in this review are: patient survival, acute graft rejection, chronic graft rejection, diabetes, graft function, graft loss, chronic graft versus host disease, acute graft versus host disease, surgical complications, infusion complications, post-transplant lymphoproliferative disease, liver function, renal function, cognition, depression, health-related quality of life, hospitalisation, high blood pressure, low blood pressure, cancer-other, cancer-skin, cardiovascular disease, bacterial infection, Epstein-Barr infection, cytomegalovirus infection, other viral infections and growth.

Liver-Metabolizing Genes and Their Relationship to the Performance of Elite Spanish Male Endurance Athletes; a Prospective Transversal Study.

BACKGROUND: The genetic profile that is needed to define an endurance athlete has been studied during recent years. The main objective of this work is to approach for the first time the study of genetic variants in liver-metabolizing genes and their role in endurance performance by comparing the allelic and genotypic frequencies in elite endurance athletes to the non-athlete population. METHODS: Genotypic and allelic frequencies were determined in 123 elite endurance athletes (75 professional road cyclists and 48 endurance elite runners) and 122 male non-athlete subjects (sedentary). Genotyping of cytochrome P450 family 2 subfamily D member 6 (CYP2D6 rs3892097), glutathione-S transferase mu isoform 1 (GSTM1), glutathione S-transferase pi (GSTP rs1695) and glutathione S-transferase theta (GSTT) genes was performed by polymerase chain reaction (PCR). The combination of the polymorphisms for the "optimal" polygenic profile has been quantified using the genotype score (GS). RESULTS: Statistical differences were found in the genetic distributions between elite endurance athletes and non-athletes in CYP2D6 (p < 0.001) and GSTT (p = 0.014) genes. The binary logistic regression model showed a favourable OR (odds ratio) of being an elite endurance runner against a professional road cyclist (OR: 2.403, 95% CI: 1.213-4.760 (p = 0.002)) in the polymorphisms studied. CONCLUSIONS: Genotypic distribution of liver-metabolizing genes in elite endurance athletes is different to non-athlete subjects, with a favourable gene profile in elite endurance athletes in terms of detoxification capacity.

Public health economic evaluation of different European Union-level policy options aimed at reducing population dietary trans fat intake.

BACKGROUND: The adverse relation between dietary trans fatty acid (TFA) intake and coronary artery disease risk is well established. Many countries in the European Union (EU) and worldwide have implemented different policies to reduce the TFA intake of their populations. OBJECTIVE: The aim of this study was to assess the added value of EU-level action by estimating the cost-effectiveness of 3 possible EU-level policy measures to reduce population dietary TFA intake. This was calculated against a reference situation of not implementing any EU-level policy (i.e., by assuming only national or self-regulatory measures). DESIGN: We developed a mathematical model to compare different policy options at the EU level: 1) to do nothing beyond the current state (reference situation), 2) to impose mandatory TFA labeling of prepackaged foods, 3) to seek voluntary agreements toward further reducing industrially produced TFA (iTFA) content in foods, and 4) to impose a legislative limit for iTFA content in foods. RESULTS: The model indicated that to impose an EU-level legal limit or to make voluntary agreements may, over the course of a lifetime (85 y), avoid the loss of 3.73 and 2.19 million disability-adjusted life-years (DALYs), respectively, and save >51 and 23 billion euros when compared with the reference situation. Implementing mandatory TFA labeling can also avoid the loss of 0.98 million DALYs, but this option incurs more costs than it saves compared with the reference option. CONCLUSIONS: The model indicates that there is added value of an EU-level action, either via a legal limit or through voluntary agreements, with the legal limit option producing the highest additional health benefits. Introducing mandatory TFA labeling for the EU common market may provide some additional health benefits; however, this would likely not be a cost-effective strategy.

A Systematic Review of Economic Evaluations of Pacemaker Telemonitoring Systems.

INTRODUCTION AND OBJECTIVES: Over the last decade, telemedicine applied to pacemaker monitoring has undergone extraordinary growth. It is not known if telemonitoring is more or less efficient than conventional monitoring. The aim of this study was to carry out a systematic review analyzing the available evidence on resource use and health outcomes in both follow-up modalities. METHODS: We searched 11 databases and included studies published up until November 2014. The inclusion criteria were: a) experimental or observational design; b) studies based on complete economic evaluations; c) patients with pacemakers, and d) telemonitoring compared with conventional hospital monitoring. RESULTS: Seven studies met the inclusion criteria, providing information on 2852 patients, with a mean age of 81 years. The main indication for device implantation was atrioventricular block. With telemonitoring, cardiovascular events were detected and treated 2 months earlier than with conventional monitoring, thus reducing length of hospital stay by 34% and reducing routine and emergency hospital visits as well. There were no significant intergroup differences in perceived quality of life or number of adverse events. The cost of telemonitoring was 60% lower than that of conventional hospital monitoring. CONCLUSIONS: Compared with conventional monitoring, cardiovascular events were detected earlier and the number or hospitalizations and hospital visits was reduced with pacemaker telemonitoring. In addition, the costs associated with follow-up were lower with telemonitoring.

Erlotinib monotherapy for the maintenance treatment of non-small cell lung cancer after previous platinum-containing chemotherapy: a NICE single technology appraisal.

The UK National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of erlotinib (Roche) to submit evidence for the clinical and cost effectiveness of erlotinib as monotherapy for the maintenance treatment of patients with non-small cell lung cancer (NSCLC) and stable disease following previous treatment with four cycles of platinum-containing therapy. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG) for this appraisal. The ERG reviewed the clinical- and cost-effectiveness evidence in two stages and in accordance with the decision problem defined by NICE. The analysis of the submitted models assessed the appropriateness of the approach taken by the manufacturer in modelling the decision problem. Analysis also included reliability of model implementation and the extent of conformity to published standards and prevailing norms of practice within the health economics modelling community. Particular attention was paid to issues likely to have substantial impact on the base-case cost-effectiveness results. Clinical evidence was derived from a multi-centre, double-blind, randomized, phase III study designed to address the overall population of NSCLC patients. Outcomes included progression-free survival (PFS) and overall survival (OS). The recruited population was mainly from outside of Western Europe and no patients in the pivotal trial had received pemetrexed as a first-line therapy, which is now accepted clinical practice in the UK. The evidence considered in this article includes only the population for whom marketing authorizations has been received--that is, patients with stable disease following first-line therapy. The trial reported a small but statistically significant increase in both PFS and OS in patients with stable disease receiving erlotinib compared with placebo. However, no significant difference was identified in OS when patients with non-squamous disease and stable disease were considered as a subgroup. The economic evidence was focussed on the ERG's assessment of three economic models that related to patients with stable disease and compared erlotinib with placebo in the squamous and non-squamous populations and erlotinib with pemetrexed in the non-squamous population. The incremental cost-effectiveness ratios (ICERs) reported by the manufacturer were £39,936 per QALY gained (stable disease, all); £35,491 per QALY gained (stable disease, squamous); and £40,020 per QALY gained (stable disease, non-squamous). In comparison with pemetrexed, in the cases where erlotinib was considered to be superior or equivalent, erlotinib dominated. In the cases where erlotinib was considered to be slightly inferior, then the ICERs ranged between £91,789 and £511,351 per QALY gained; these ICERs appear in the south-west corner of a cost-effectiveness plane, i.e. erlotinib is cheaper but less effective than pemetrexed. The ERG recalculated the base-case cost-effectiveness results in the manufacturer's submission, considering nine key areas where corrections and/or adjustments were required, related to time horizon, discounting logic, costs of erlotinib and pemetrexed, cost of second-line chemotherapy, unit costs, utility values, PFS and OS. This resulted in ERG-revised ICERs for the stable disease squamous population of £44,812 per QALY gained, in the stable disease non-squamous population of £68,120 per QALY gained, and, when erlotinib was compared with pemetrexed, the result was £84,029 per QALY gained. All values were above NICE's perceived willingness-to-pay threshold. After the second Appraisal Committee meeting, the Committee did not recommend the use of erlotinib in this patient population.

[Effectiveness of spinal manipulation in treating whiplash injuries]. / Efectividad de las técnicas de manipulación espinal en la "lesión por latigazo" (whiplash).

OBJECTIVE: To assess the efficacy of spinal manipulation treatments in patients with whiplash injuries. DESIGN: Systematic review. DATA SOURCES: A systematic search was conducted between January 2000 and May 2006 in CINAHL, the Cochrane Library, EMBASE, MEDLINE, CRD (Center for Reviews and Dissemination), Spanish Index Medicus, and PEDro. Reports of Physiotherapy congresses between 2000 and 2005 were reviewed. INCLUSION CRITERIA: studies of patients with whiplash injuries who were treated with spinal manipulations, either exclusively or combined with other therapies. Outcomes were expressed in at least one of the following: pain, global perceived effect or range of movement (ROM). Only 9 of the first screening (290) were analyzed. DATA EXTRACTION: The studies were independently selected by 2 reviewers. Methodological quality was assessed on the basis of the recommendations of the Agency for Health Technology Evaluation. The lack of data and their heterogeneity made any statistical analysis impossible. RESULTS: Of the 9 studies analyzed, 7 were systematic reviews and 2 were primary studies. No review showed evidence of the efficacy of spinal manipulations versus other therapies. The results were often explained vaguely and inadequately. CONCLUSIONS: There is not enough evidence to suggest that spinal manipulation is an effective treatment for whiplash. Though in the short term it seems to improve pain, any long-term benefit or clinical or economic advantages versus conventional therapies could not be determined.