Three-year analysis of results, safety and progression in patients with open-angle glaucoma or ocular hypertension, undertaking trabecular microsurgery.

AIM: To evaluate the efficacy, safety, structural and functional progression following the insertion of iStent inject ® implants in patients with open-angle glaucoma or ocular hypertension at a tertiary-level hospital. MATERIALS AND METHODS: A retrospective study included 98 eyes (57 males and 41 females) with open-angle glaucoma or ocular hypertension, which underwent iStent inject W® implantation (Glaukos, Corporation, CA) between December 2018 and December 2022. Differences in intraocular pressure (IOP), the number of hypotensive eye drops used, and structural and functional tests were assessed between preoperative values and subsequent reviews during a follow-up period of one (n = 98), two (n = 55), and three years (n = 15) after surgery. RESULTS: Among the 98 eyes studied, 85% were diagnosed with open-angle glaucoma (50% mild, 32% moderate, and 18% severe) and 15% with ocular hypertension. There was a statistically significant reduction in IOP compared to preoperative values for all visits except the 1-month (p = 0.36) and 3-year (p = 0.39) visits. Visual acuity increased from 0.39 ±â€¯0.25 to 0.72 ±â€¯0.24 (p < 0.01), considering that a significant portion of the interventions included cataract surgery. Before surgery, 66% of the sample used 2 or more hypotensive medications. Post-surgery, the number of hypotensive medications decreased (from 1.88 ±â€¯0.84 to 0.21 ±â€¯0.59 at 3 years) (p < 0.01), with an 88.9% reduction in the number of medications over three years. After surgery, 75% of cases did not require any medication. Regarding structural and functional tests, thickness of retinal nerve fiber layers (RNFL (p = 0.35), excavation / papilla ratio E/P (p = 0.31), visual function index (VFI (p = 0.06), and deviation mean (MD (p = 0.06) showed no statistically significant differences post-intervention. However, standard deviation of the pattern (DSM) did exhibit differences, decreasing from 5.46 ±â€¯4.03 dB to 5.34 ±â€¯3.48 dB (p = 0.02). CONCLUSION: The results of this study suggest that the iStent inject W® technique constitutes an effective and safe option for tension control and glaucoma treatment.

Correction: Chua et al. Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore. Cancers 2023, 15, 1812.

The authors wish to revise two words in Table 1 row 3, and the first paragraph of Section 2 [...].

Cost-Effectiveness Analysis of HPV Extended versus Partial Genotyping for Cervical Cancer Screening in Singapore.

Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30-69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method.

Metal-organic frameworks and covalent organic frameworks as disruptive membrane materials for energy-efficient gas separation.

In this Review we survey the molecular sieving behaviour of metal-organic framework (MOF) and covalent organic framework (COF) membranes, which is different from that of classical zeolite membranes. The nature of MOFs as inorganic-organic hybrid materials and COFs as purely organic materials is powerful and disruptive for the field of gas separation membranes. The possibility of growing neat MOFs and COFs on membrane supports, while also allowing successful blending into polymer-filler composites, has a huge advantage over classical zeolite molecular sieves. MOFs and COFs allow synthetic access to more than 100,000 different structures and tailor-made molecular gates. Additionally, soft evacuation below 100 °C is often enough to achieve pore activation. Therefore, a huge number of synthetic methods for supported MOF and COF membrane thin films, such as solvothermal synthesis, seed-mediated growth and counterdiffusion, exist. Among them, methods with high scale-up potential, for example, layer-by-layer dip- and spray-coating, chemical and physical vapour deposition, and electrochemical methods. Additionally, physical methods have been developed that involve external stimuli, such as electric fields and light. A particularly important point is their ability to react to stimuli, which has allowed the 'drawbacks' of the non-ideality of the molecular sieving properties to be exploited in a completely novel research direction. Controllable gas transport through membrane films is a next-level property of MOFs and COFs, leading towards adaptive process deviation. MOF and COF particles are highly compatible with polymers, which allows for mixed-matrix membranes. However, these membranes are not simple MOF-polymer blends, as they require improved polymer-filler interactions, such as cross-linking or surface functionalization.

Leveraging DICE (Discretely-Integrated Condition Event) Simulation to Simplify the Design and Implementation of Hybrid Models.

OBJECTIVES: Using an example of an existing model constructed by the National Institute for Health and Care Excellence (NICE) to inform a real health technology assessment, this study seeks to demonstrate how a discretely integrated condition event (DICE) simulation can improve the implementation of Markov models. METHODS: Using the technical report and spreadsheet, the original model was translated to a standard DICE simulation without making any changes to the design. All original analyses were repeated and the results were compared. Aspects that could have improved the original design were then considered. RESULTS: The original model consisted of 32 copies (8 risk strata × 4 treatments) of the Markov structure, containing more than 6000 Microsoft Excel® formulas (18 MB files). Three aspects (nonadherence, scheduled treatment stop, and end of fracture risk) were handled by incorporating weighted averages into the cycle-specific calculations. The DICE implementation used 3 conditions to represent the states and a single transition event to apply the probabilities; 3 additional events processed the special aspects, and profiles handled the 8 strata (0.12 MB file). One replication took 16 seconds. The original results were reproduced but extensive additional sensitivity analyses, including structural analyses, were enabled. CONCLUSION: Implementing a real Markov model using DICE simulation both preserves the advantages of the approach and expands the available tools, improving transparency and ease of use and review.

Cancer-ID: Toward Identification of Cancer by Tumor-Derived Extracellular Vesicles in Blood.

Extracellular vesicles (EVs) have great potential as biomarkers since their composition and concentration in biofluids are disease state dependent and their cargo can contain disease-related information. Large tumor-derived EVs (tdEVs, >1 µm) in blood from cancer patients are associated with poor outcome, and changes in their number can be used to monitor therapy effectiveness. Whereas, small tumor-derived EVs (<1 µm) are likely to outnumber their larger counterparts, thereby offering better statistical significance, identification and quantification of small tdEVs are more challenging. In the blood of cancer patients, a subpopulation of EVs originate from tumor cells, but these EVs are outnumbered by non-EV particles and EVs from other origin. In the Dutch NWO Perspectief Cancer-ID program, we developed and evaluated detection and characterization techniques to distinguish EVs from non-EV particles and other EVs. Despite low signal amplitudes, we identified characteristics of these small tdEVs that may enable the enumeration of small tdEVs and extract relevant information. The insights obtained from Cancer-ID can help to explore the full potential of tdEVs in the clinic.

Prevalence of hypotension in hypertensive treated patients within the Primary Care setting. The PRESCAP 2010 study.

OBJECTIVE: To determine the prevalence of hypotension and associated factors in hypertensive patients treated in the Primary Care setting. MATERIALS AND METHODS: A cross-sectional, descriptive, and multicentre study was conducted with a total of 2635 general practitioners consecutively including 12,961 hypertensive patients treated in a Primary Care setting in Spain. An analysis was performed on the variables of age, gender, weight, height, body mass index, waist circumference, cardiovascular risk factors (diabetes, dyslipidaemia, smoking, obesity, sedentary lifestyle), fasting plasma glucose, complete lipid profile, as well as the presence of target organ damage (left ventricular hypertrophy, microalbuminuria, carotid atherosclerosis) and associated clinical conditions. Hypotension was defined as a systolic blood pressure less than 110mmHg or a diastolic blood pressure less than 70mmHg. A multivariate analysis was performed to determine the variables associated with the presence of hypotension. RESULTS: The mean age was 66.2 years, and 51.7% of patients were women. The mean time of onset of hypertension was 9.1 years. A total of 13.1% of patients (95% confidence interval 12.4-13.6%) had hypotension, 95% of whom had low diastolic blood pressure. The prevalence of hypotension was higher in elderly patients (25.7%) and in those individuals with coronary heart disease (22.6%). The variables associated with the presence of hypotension included a history of cardiovascular disease, being treated with at least 3 antihypertensive drugs, diabetes, and age. CONCLUSIONS: One out of 4-5 elderly patients, or those with cardiovascular disease, had hypotension. General practitioners should identify these patients in order to determine the causes and adjust treatment to avoid complications.

[Risk of falls and drug use in patients over 65 years of age. The PYCAF study]. / Riesgo de caídas y consumo de fármacos en los pacientes mayores de 65 años. Estudio PYCAF.

OBJECTIVE: To evaluate the risk of falls and its relationship with the multiple drug use in the non-institutionalised elderly. MATERIALS AND METHODS: The PYCAF study (Prevalence and Characteristics of the Fragile Elderly) is a cross-sectional, descriptive and multicentre study in patients> 65 years of age. A fall was considered high risk when it took more than 20seconds to perform the Timed Up and Go test. Consuming between 5 and 9 drugs is considered multiple drug (MD) use, and extreme multiple drug (EMD) use the consumption of 10 or more drugs. Adjusted logistic regression models evaluated the association between multiple drug use and EMD and the risk of falls. RESULTS: A total of 2,461 patients (57.9% women), with a mean age (SD) 76.0 (± 7.0) years, were included in the study. The mean consumption of medications was 6.6 ± 3.7, range 0-23. Multiple drug use was present in 50.6%, and EMD in 19.2% of patients. A high risk of falls was observed in 13.7% of patients. The prevalence of high risk of falls was more than 2times higher in patients with EMD (ORa = 2.07, 95% CI = 1.27 - 3.38) and MD (ORa = 1.95, 95% CI = 1.26 - 2.99). CONCLUSIONS: MD and EMD are associated with a high risk of falls in patients over 65 years of age. The risk of falls in elderly patients should be assessed before prescribing medication.

[Social reimbursement-the Spanish-German ENT Society's (SDGHNO) Latin America project]. / Soziale Rückvergütung ­ das Projekt "Lateinamerika" der Spanisch-Deutschen HNO-Gesellschaft (SDGHNO).

Nowadays, social projects are usually oriented in such a way that after a given period of time, they can either support themselves independently or even allow a pecuniary reimbursement. In the latter case, experts speak of a profit-oriented reimbursement. On the other hand, there is so-called social reimbursement, which in contrast to the abovementioned form is not profit oriented, but, for example, considers its task fulfilled by the fact of successful knowledge transfer. The Spanish-German Society for ENT Medicine and Head and Neck Surgery (SDGHNO) launched the Latin America project in 2001 under the patronage of the then President Prof. Dr. Wolfgang Draf (Fulda). The goal of the SDGHNO was and is to create a professional as well as cultural platform for Spanish- and German-speaking ENT doctors. This platform can and should be used for professional purposes, e.g., for knowledge transfer. Since the beginning of its existence, the Latin America project has thus brought numerous scientific events into being and created specific contacts which have lasted until today or have even been continued and further developed. Particularly successful examples are Chile, Colombia, and Peru. This is a vivid example of social reimbursement, because the participating German-speaking members/speakers carried out their tasks on an entirely voluntary basis. Thus, the SDGHNO did not bear any travel, catering, or accommodation costs. The activities of the SDGHNO within the framework of the Latin America project are explained.

[Prevalence of obesity and cardiovascular comorbidity associated in patients included in the IBERICAN study]. / Prevalencia de obesidad y comorbilidad cardiovascular asociada en los pacientes incluidos en el estudio IBERICAN (Identificación de la poBlación Española de RIesgo CArdiovascular y reNal).

OBJECTIVES: To analyse the prevalence of obesity and its association with other cardiovascular risk factors and cardiovascular disease in a sample of patients from the (Identification of the Spanish population at cardiovascular and renal risk) IBERICAN study. MATERIAL AND METHODS: Analysis of the inclusion visit of the first 5,013 patients of the IBERICAN longitudinal, observational, and multicentre study in which individuals aged 18 to 85 years were included in Primary Care Clinics in the different regions of Spain. In this work obesity was defined as a body mass index ≥ 30kg/m2. RESULTS: The prevalence of obesity was 35.7% (95% CI: 35.0-36.4%), of which 36.6% were men and 34.9% were women (P=0.214), and significantly increasing with age (0.001). The obesity had the associated higher prevalence of hypertension (62.8% vs. 39.4%, P<001), dyslipidaemia (56.9% vs. 47.1%, P<0.001), sedentary lifestyle (40.6% vs. 24.6%, P<.001), diabetes (27.5% vs. 14.8%, P<.001), hyperuricaemia (23.6% vs. 12.7%, P<.001), subclinical organ injury (33.7% vs. 26.5%, P<.001) and cardiovascular disease (21.2% vs. 15.3%, P<.001). The multivariate analysis showed that the variables associated with obesity were: arterial hypertension (P<.001), hyperuricemia (P<.001), sedentary lifestyle (P<.001), diabetes mellitus (P<0.001), age (P<0.001), low educational level (P<0.001) and lower consumption of tobacco (P<0.001). CONCLUSIONS: The analysis of the IBERICAN study shows that approximately one third of the analysed population meets criteria of obesity and cardiovascular risk factors. Target organ damage and cardiovascular disease were more frequent in obese patients.

[Clinical and socio-sanitary characteristics in adults older than 65 years attended in the Primary Care setting. The PYCAF study]. / Características clínicas y sociosanitarias en mayores de 65 años asistidos en atención primaria. Estudio PYCAF.

OBJECTIVE: To describe the clinical and socio-sanitary characteristics of adults older than 65 years attended in a Primary Care setting. MATERIAL AND METHODS: The PYCAF study (Prevalence and Characteristics of the Fragile Elderly) is a descriptive, cross-sectional and multicentre study, in which patients older than 65 years attended in clinical practice in Primary Care in Spain were consecutively included. RESULTS: A total of 2,461 patients (mean age 76.0±6.9 years, 57.9% women) were included in the study. The coexistence of cardiovascular risk factors and comorbidities was frequent, with arterial hypertension (73.7%) being the most prevalent, followed by dyslipidaemia (58.3%), arthrosis (56.4%), obesity (34.0%), and diabetes (28.9%). Some degree of cognitive impairment was observed in 13.4% of patients. Women had higher rates of frailty (61.0% vs. 51.8%; P<.001). Just under half (47.4%) of subjects were taking more than 6 drugs, with the prescription being higher in women (44.2% vs. 49.8%; P=.047). Just under half (49.5%) of patients made more than 10 visits to Primary Care, 25.9% of patients 4 or more visits to the specialist, and 22.3% of patients were admitted to hospital in the last year. CONCLUSIONS: The PYCAF study shows that elderly patients have a higher prevalence of chronic cardiovascular and non-cardiovascular diseases, which leads to high polypharmacy. The latter has consequences both on patient safety and on the direct and indirect costs of the National Health System that emanate from the care of patients over 65 years of age. Half the sample has fragility.

Report From the First and Second Spanish Killer Immunoglobulin-Like Receptor Genotyping Workshops: External Quality Control for Natural Killer Alloreactive Donor Selection in Haploidentical Stem Cell Transplantation.

An important factor affecting the success in the setting of related haploidentical hematopoietic stem cell transplantation (HSCT) is the graft-versus-leukemia effect mediated by natural killer (NK) cells when the donor displays NK alloreactivity versus the recipient. NK cell function is regulated by killer immunoglobulin-like receptors (KIR) and it has been described that donor KIR genotype influences transplantation outcome. This has led to a requirement of laboratories to have a quality assurance program for validation and control of their KIR genotyping methods. The goal of the 1st and 2nd Spanish KIR Genotyping Workshops was to provide an external proficiency testing program in KIR genotyping for Spanish immunology and transplant laboratories. These workshops were conducted during the years 2014-2016 and consisted of 17 participating laboratories typing a set of 20 samples. The presence/absence of 16 mandatory KIR loci (2DL1, 2DL2, 2DL3, 2DL4, 2DL5, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 2DP1, 3DL1, 3DL2, 3DL3, 3DS1, and 3DP1) was evaluated per sample. Methods for KIR genotyping included polymerase chain reaction with the use of sequence-specific primers and sequence-specific oligoprobes. Consensus typing was reached in all samples, and the performance of laboratories in external proficiency testing was satisfactory in all cases. The polymorphism detected in the small sample studied in both workshops is indicative of an ample variety of KIR gene profiles in the Spanish population.

Markers of iron metabolism in retired racing Greyhounds with and without osteosarcoma.

BACKGROUND: Greyhounds have well-described clinicopathologic idiosyncrasies, including a high prevalence of osteosarcoma (OSA). Hematocrit, HGB, and HGB oxygen affinity are higher than in other dogs, while haptoglobin concentration is lower, so we hypothesized that Greyhounds have a different iron metabolism. To our knowledge, there are no reports on serum iron profiles in Greyhounds. OBJECTIVES: To elucidate iron metabolism in Greyhounds, we wanted to compare serum iron concentration, total iron-binding capacity (TIBC), and percent transferrin saturation (%SAT) in healthy retired racing Greyhounds (RRGs) with OSA (RRGs - OSA), and also with non-Greyhounds (NGs), without and with OSA (NGs - OSA). METHODS: Serum iron concentration and unsaturated iron-binding capacity (UIBC) were measured by standard methods, and TIBC and %SAT were calculated in RRGs (n = 25), RRGs - OSA (n = 28), NGs (n = 30), and NGs - OSA (n = 32). RESULTS: TIBC was lower in RRGs than in NGs (P < .0001), and in RRGs - OSA than in NGs - OSA (P < .0001). NGs - OSA had lower TIBC than healthy NGs (P = .003). Percent SAT was higher in RRGs than in NGs (P < .0001) and in RRGs - OSA (P = .008), and %SAT was also lower in NGs than in NGs - OSA (P = .004). Percent SAT was also higher in RRGs - OSA than in NGs - OSA (P = .001). Both RRGs - OSA (P = .02) and NGs - OSA (P < .0001) had lower serum iron concentrations than their healthy counterparts. CONCLUSION: Lower TIBC and higher %SAT may constitute another Greyhound idiosyncrasy compared with other dogs. In this study, all dogs with OSA had higher serum iron concentrations and %SAT than healthy dogs.

Treating acetaminophen overdose: thresholds, costs and uncertainties.

The United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) modified the indications for N-acetylcysteine therapy of acetaminophen (paracetamol) overdose in September 2012. The new treatment threshold line was lowered to 100 mg/L (662 µmol/L) for a 4 hours acetaminophen concentration from the previous 200 mg/L (1325 µmol/L). This decision has the potential to substantially increase overall costs associated with acetaminophen overdose with unclear benefits from a marginal increase in patients protected from hepatotoxicity, fulminant hepatic failure, death, or transplant. Changing the treatment threshold for acetaminophen overdose also implies that ingestion amounts previously thought not to require acetaminophen concentration measurements would need to be revised. As a result, more individuals will be sent to hospitals in order that everyone with a predicted 4 hours concentration above the 100 mg/L line will have concentrations measured and potentially be treated with N-acetylcysteine. Before others consider adopting this new treatment guideline, formal cost-effectiveness analyses need to be performed to define the appropriate thresholds for referral and treatment.

Adjusting for patient crossover in clinical trials using external data: a case study of lenalidomide for advanced multiple myeloma.

OBJECTIVES: In some trials, particularly in oncology, patients whose disease progresses under the comparator treatment are crossed over into the experimental arm. This unplanned crossover can introduce bias in analyses because patients who crossover likely have a different prognosis than those who do not cross over; for instance, sicker patients not responding to standard therapy or those expected to benefit the most may be selectively chosen to receive the experimental treatment. Standard statistical methods cannot adequately correct for this bias. We describe an approach designed to minimize the impact of crossover, and illustrate this by using data from two randomized trials in multiple myeloma (MM). METHODS: The MM-009/010 trials compared lenalidomide and high-dose dexamethasone (Len+Dex) with dexamethasone alone (Dex). Nearly half (47%) of the patients randomized to Dex crossed over to Len with or without Dex (Len+/-Dex) at disease progression or study unblinding. Data from these trials was used to predict survival in an economic model evaluating the cost-effectiveness of lenalidomide. To adjust for crossover, the prediction equations were calibrated to match survival with Dex or Dex-equivalent therapies in trials conducted by the Medical Research Council (MRC) in the United Kingdom. To adjust for differences between the MM and MRC trial populations, a prediction equation was developed from the MRC data and used to predict survival by setting predictors to mean values for patients in the MM-009/010 trials. The expected survival with Dex without crossover was then predicted from the calibrated MM-009/010 equation (i.e., adjusted to match survival predicted from the MRC equation). RESULTS: The adjusted median overall survival predicted by the MRC equation was 19.5 months (95%CI, 16.6-22.9) for patients with one prior therapy, and 11.6 months (95% CI, 9.5-14.2) for patients with >1 prior therapy. These estimates are considerably shorter than was observed in the clinical trials: 33.6 months (27.1-NE) and 27.3 months (95% CI, 23.3-33.3) as of December 2005. CONCLUSION: The calibration method described here is simple to implement, provided that suitable data are available; it can be implemented with other types of endpoints in any therapeutic area.

A discrete-event simulation of smoking-cessation strategies based on varenicline pivotal trial data.

BACKGROUND: Smoking is the leading cause of preventable death in the US. While one in five individuals smoke, and 70% of these indicate a desire to quit, <5% of unaided quit attempts succeed. Cessation aids can double or triple the odds of successfully quitting. Models of smoking-cessation behaviour can elucidate the implications of individual abstinence patterns to allow better tailoring of quit attempts to an individual's characteristics. OBJECTIVE: The objectives of this study were to develop and validate a discrete-event simulation (DES) to evaluate the benefits of smoking abstinence using data from the pooled pivotal clinical trials of varenicline versus bupropion or placebo for smoking cessation and to provide a foundation for the development of a lifetime smoking-cessation model. METHODS: The DES model simulated the outcome of a single smoking-cessation attempt over 1 year, in accordance with the clinical trial timeframes. Pharmaceutical costs were assessed from the perspective of a healthcare payer. The model randomly sampled patient profiles from the pooled varenicline clinical trials. All patients were physically and mentally healthy adult smokers who were motivated to quit abruptly. The model allowed for comparisons of up to five distinct treatment approaches for smoking cessation. In the current analyses, three interventions corresponding to the clinical trials were evaluated, which included brief counselling plus varenicline 1.0 mg twice daily (bid) or bupropion SR 150 mg bid versus placebo (i.e. brief counselling only). The treatment periods in the clinical trials were 12 weeks (target quit date: day 8), with a 40-week non-treatment follow-up, and counselling continuing over the entire 52-week period in all treatment groups. The main outcome modelled was the continuous abstinence rate (CAR; defined as complete abstinence from smoking and confirmed by exhaled carbon monoxide ≤ 10 ppm) at end of treatment (weeks 9-12) and long-term follow-up (weeks 9-52), and total time abstinent from smoking over the course of 52 weeks. The model also evaluated costs and cost-effectiveness outcomes. RESULTS: For the varenicline, bupropion and placebo cohorts, respectively, the model predicted CARs for weeks 9-12 of 44.3%, 30.4% and 18.6% compared with observed rates of 44.0%, 29.7% and 17.7%; over weeks 9-52, predicted CARs in the model compared with observed rates in the pooled clinical studies were 22.9%, 16.4% and 9.4% versus 22.4%, 15.4% and 9.3%, respectively. Total mean abstinence times accrued in the model varenicline, bupropion and placebo groups, respectively, were 3.6, 2.6 and 1.5 months and total pharmaceutical treatment costs were $US261, $US442 and $US0 (year 2008 values) over the 1-year model period. Using cost per abstinent-month achieved as a measure of cost effectiveness, varenicline dominated bupropion and yielded an incremental cost-effectiveness ratio of $US124 compared with placebo. CONCLUSION: The model accurately replicated abstinence patterns observed in the clinical trial data using individualized predictions and indicated that varenicline was more effective and may be less costly than bupropion. This simulation incorporated individual predictions of abstinence and relapse, and provides a framework for lifetime modelling that considers multiple quit attempts over time in diverse patient populations using a variety of quit attempt strategies.

The efficiency frontier approach to economic evaluation of health-care interventions.

BACKGROUND: IQWiG commissioned an international panel of experts to develop methods for the assessment of the relation of benefits to costs in the German statutory health-care system. PROPOSED METHODS: The panel recommended that IQWiG inform German decision makers of the net costs and value of additional benefits of an intervention in the context of relevant other interventions in that indication. To facilitate guidance regarding maximum reimbursement, this information is presented in an efficiency plot with costs on the horizontal axis and value of benefits on the vertical. The efficiency frontier links the interventions that are not dominated and provides guidance. A technology that places on the frontier or to the left is reasonably efficient, while one falling to the right requires further justification for reimbursement at that price. This information does not automatically give the maximum reimbursement, as other considerations may be relevant. Given that the estimates are for a specific indication, they do not address priority setting across the health-care system. CONCLUSION: This approach informs decision makers about efficiency of interventions, conforms to the mandate and is consistent with basic economic principles. Empirical testing of its feasibility and usefulness is required.

Economic evaluation of doripenem for the treatment of nosocomial pneumonia in the US: discrete event simulation.

OBJECTIVE: Patients with nosocomial pneumonia, particularly associated with ventilator use, are at an increased risk of death and further morbidity. Doripenem is a new broad-spectrum carbapenem that is approved for complicated intra-abdominal infection and complicated urinary tract infection and is under the Food and Drug Administration (FDA)'s review for nosocomial pneumonia and ventilator-associated pneumonia in the United States (US). The economic implications of this new antibiotic, relative to imipenem for treatment of nosocomial pneumonia, were investigated. RESEARCH DESIGN AND METHODS: An economic model of the clinical course of nosocomial pneumonia after initiation of treatment was developed using discrete event simulation. Pairs of identical patients are generated; one receives doripenem and the other receives imipenem. Their clinical course is simulated using clinical trial data on treatment response, seizure rates, mortality, length of hospital and intensive care unit stays, days on mechanical ventilation, and emerging Pseudomonas aeruginosa (PsA) resistance; published treatment and hospital costs; and PsA transmission risk. Analyses of 10,000 patients per treatment for 100 replications were performed. From the perspective of a comprehensive payer, costs - in 2007 US Dollars (USDs) - were estimated for a treatment episode (35-49 days) without discounting. Study limitation includes clinical trial-driven design of the model in which some aspects may not represent actual practice; some assumptions around efficacy data due to data unavailability; and lack of consideration of factors that impact disease transmission such as hospital environment, hospital size, and hospital infection control as these analyses were not intended for any specific healthcare institution. RESULTS: Doripenem yielded an average of approximately $7000 in savings per patient compared to imipenem, with 95% driven by reduction in hospital length of stay. The model predicted 63% fewer seizures, 52% fewer emerging PsA resistance, and 15% shorter stays leading to 46% fewer transmissions associated with doripenem. CONCLUSION: Using doripenem for treatment of nosocomial pneumonia is expected to yield significant savings compared to imipenem use in the US.

[Surgical and nutritional evaluation of children with percutaneous endoscopic gastrostomy]. / Evaluación quirúrgica y nutricional de los niños con gastrostomía endoscópica percutánea.

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) has suppoused an improvement in the nutritional management of patients with deglution difficulty. Surgical and nutritional aspects have been evaluated in our patients with PEG. MATERIAL AND METHODS: A descriptive retrospective study with individual analysis of surgical, nutritional and satisfaction items has been developed. RESULTS: 83 PEG (1994-08) have been implanted in neurological patients (63.8%) followed by cystic fibrosis; Mean age 7 years (4 months-25 years). Two patients have a ventriculo-peritoneal shunt (VPS) and 3 a peritoneal dialysis catheter (PDC). 12% had a mild complication and 3 patients a severe one, with 2 reinterventions performed. 40 patients have the dispositive, 25 were removed after a mean follow-up of 2,5 years and 17 patients dies. Nutrition was done with initial, continuation or specials formulas. Weight evaluation was satisfactory in 96% of patients and biochemical indicators were normalized in 97% of them. Satisfaction is very high among the majority of parents. CONCLUSIONS: PEG is a technique that allows nutritional recuperation with few surgical complications. VPS and PDC are not contraindications for the percutaneous gastrostomy. PEG improves children and relatives life quality.