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PubMedDate not supplied

Pneumatic dilation versus intrasphincteric botulinum toxin injection in the treatment of achalasia cardia in India: an economic analysis.

BACKGROUND: Pneumatic dilation (PD) is an established therapeutic option for achalasia cardia. Recently, intrasphincteric botulinum toxin (BT) has been used to treat achalasia cardia in view of its simplicity and safety. However, it is likely to be a costly treatment as repeated injections are often needed due to its short-lasting effect. No economic analysis of PD and BT strategies has been done in India. METHODS: A decision tree was constructed using decision analysis software (DATA 4.0; TreeAge Software, Williamstown, MA, USA). Probability estimates for BT injection and PD (and, in case of failure, surgery) were obtained from published literature, preferably from India. Direct "out-of-pocket" costs (in Indian rupees; currently US$ 1 = 49 rupees approximately) for baseline analysis were obtained from our hospital and from some private hospitals. Sensitivity analysis was done using a wide range of probability and cost estimates. RESULTS: Intrasphincteric BT injection strategy was more costly at 18,520 rupees per patient than PD strategy (4,568 rupees), yielding an incremental cost of 13,952 rupees per patient successfully treated. Sensitivity analysis supported the conclusions of the baseline analysis. CONCLUSION: Primary intrasphincteric BT injection strategy was costlier than primary PD strategy in the treatment of achalasia cardia in India, and therefore cannot be justified despite its efficacy, relative ease of administration and safety.

Aged↗

PubMed2003

Pharmacoeconomic analysis of osteoporosis treatment with risedronate.

Hip fracture is an important and costly problem. Therapy with the bisphosphonate risedronate effectively prevents hip and other fractures among women with established osteoporosis. Risedronate is a first-choice therapy option in the German Guidelines of the Dachverband Osteologie for Osteoporosis according to evidence-based medicine criteria for the treatment of postmenopausal osteoporosis, osteoporosis of the elderly (women aged > 75 years) and glucocorticoid-induced osteoporosis. There are few published economic evaluations of bisphosphonates in Germany. Therefore, an assessment of the cost-effectiveness of risedronate utilizing a state transition Markov model of established postmenopausal osteoporosis based on randomized clinical trial data was developed. Uncertainty underlying model parameters and outcomes was dealt with using traditional sensitivity analysis and stochastic sensitivity analysis to produce quasi-95% Cls. We focused on patients aged 70 years, since this population most closely matches the randomized controlled trial and is typical of osteoporosis patients in Germany. The baseline model was a cohort of 1,000 70-year-old women, who received risedronate for 3 years and were followed up for an overall observation period of 10 years, modelling transitions through estimated health states and evaluating outcomes. Over the 3-year treatment period and 10-year observation period, risedronate dominated the current average basic treatment in Germany. In the risedronate group 33 hip fractures were averted and 32 quality-adjusted life years (QALYs) were gained (discounted values). Risedronate treatment saves costs for German social insurance: the present net value of the associated costs from the perspective of German social insurance is [symbol: see text]10.66 million if risedronate treatment is used versus [symbol: see text]11 million if basic treatment is used. Thus, net savings of [symbol: see text]340,000 for the treatment group per 1,000 treated women were calculated. Furthermore, risedronate treatment is cost effective from the perspective of the statutory health insurance with costs per averted hip fracture in the analyzed population of [symbol: see text]33,856 and cost per QALY gained of [symbol: see text]35,690. Both results demonstrate cost-effectiveness and are far below the accepted threshold level of [symbol: see text]50,000. Based on this analysis, risedronate is a cost-effective treatment for postmenopausal osteoporosis within the German health care system, offering benefits for osteoporotic patients and for budget decision-makers.

Aged↗

PubMed2002

Diagnosis of Wihipple disease by immunohistochemical analysis: a sensitive and specific method for the detection of Tropheryma whipplei (the Whipple bacillus) in paraffin-embedded tissue.

Whipple disease is a rare infection characterized clinically by diarrhea, fever, weight loss, arthralgia, malabsorption, and other systemic manifestations. The etiologic agent, Tropheryma whipplei, has been cultured only rarely. By using a polyclonal rabbit antibody produced against a cultured strain of T whipplei, tissue sections from 18 patients with Whipple disease were studied. Specimens from patients with histologic mimics and other infections served as control specimens. Immunostaining was identified in all 18 patients. Granular immunostaining was observed similar to that in periodic acid-Schiff (PAS) stains. In 2 patients, immunostaining was identified in specimens negative by H&E and PAS stains. In 4 patients studied before and after antibiotic therapy, immunostaining was retained but diminished in intensity and quantity. Immunostaining was not identified in any control specimen. Immunohistochemical analysis is a sensitive and specific method for the diagnosis of Whipple disease in paraffin-embedded tissue and may provide new opportunities to investigate the pathogenesis of the infection.

Actinobacteria↗

PubMed2006

Identifying patients at risk of nursing home admission: The Leeds Elderly Assessment Dependency Screening tool (LEADS).

BACKGROUND: Discharge from hospital to a nursing home represents a major event in the life of an older person and should only follow a comprehensive functional and medical assessment. A previous study identified 3 dependency scales able to discriminate across outcomes for older people admitted to an acute setting. We wished to determine if a single dependency scale derived from the 3 scales could be created. In addition could this new scale with other predictors be used as a comprehensive tool to identify patients at risk of nursing home admission. METHODS: Items from the 3 scales were combined and analysed using Rasch Analysis. Sensitivity and specificity analysis and ROC curves were applied to identify the most appropriate cut score. Binary logistic regression using this cut-off, and other predictive variables, were used to create a predictive algorithm score. Sensitivity, specificity and likelihood ratio scores of the algorithm scores were used to identify the best predictive score for risk of nursing home placement. RESULTS: A 17-item (LEADS) scale was derived, which together with four other indicators, had a sensitivity of 88% for patients at risk of nursing home placement, and a specificity of 85% for not needing a nursing home placement, within 2 weeks of admission. CONCLUSION: A combined short 17-item scale of dependency plus other predictive variables can assess the risk of nursing home placement for older people in an acute care setting within 2 weeks of admission. This gives an opportunity for either early discharge planning, or therapeutic intervention to offset the risk of placement.

Aftercare↗

PubMed2004

99mTc-HMPAO-leukocyte scintigraphy in patients with symptomatic total hip or knee arthroplasty: improved diagnostic accuracy by means of semiquantitative evaluation.

UNLABELLED: The aim of this study was to evaluate the diagnostic value, in suspected infectious prostheses, of (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) leukocyte scintigraphy interpreted with the addition of a semiquantitative analysis. METHODS: By means of a retrospective review, we included a group of 78 consecutive patients with suspected hip or knee prosthesis infection. We performed 91 (99m)Tc-HMPAO-leukocyte scintigraphies and examined 95 localizations that were suspect. Images were acquired at 3 different time points after the injection of the labeled leukocytes: 50 min (early images), 4 h, and 24 h (late images). The scintigraphic examinations were independently evaluated by 3 observers; qualitative and semiquantitative analyses were performed. The final diagnosis of infection was based on surgical, histologic, and bacteriologic data and follow-up. RESULTS: On qualitative analysis, sensitivity, specificity, and accuracy were 80.4%-87%, 65.3%-71.4%, and 75.8%-77.9%, respectively. On semiquantitative analysis, sensitivity, specificity, and accuracy were 95.6%, 95.8%, and 95.8%, respectively. The analysis of 95% confidential intervals showed statistically significant differences in specificity and accuracy between semiquantitative and qualitative analyses. CONCLUSION: In those patients who underwent (99m)Tc-HMPAO-leukocyte scintigraphy for suspected hip or knee prosthesis infection, the addition of a semiquantitative evaluation to the qualitative analysis of early and late images leads to a significant improvement in both specificity and accuracy.

Adult↗

PubMed2001

Validation of an outcomes instrument for tonsil and adenoid disease.

OBJECTIVE: To design and validate a disease-specific health status instrument-the Tonsil and Adenoid Health Status Instrument-for use in children with tonsil and adenoid disease. DESIGN: Prospective psychometric and clinimetric instrument validation in 3 stages. SETTINGS: A tertiary academic pediatric specialty hospital and a tertiary academic hospital, in 2 different cities. PATIENTS/OTHER PARTICIPANTS: Children with tonsil and adenoid disease presenting for evaluation and treatment (n = 224). INTERVENTION/METHOD: Prospective instrument validation. Stage 1 consisted of initial item testing, reduction, and subscale construction; stage 2, reliability and validity testing, factor analysis, and final item reduction; and stage 3, responsiveness analysis. MAIN OUTCOME MEASURES: Test-retest and internal consistency reliability; content, construct, and criterion validity; orthogonal principal components factor analysis; and response sensitivity analysis. RESULTS: Factor analysis and item analysis confirmed 6 distinct subscales measuring different constructs (aspects) of disease-specific health status that are affected by tonsil and adenoid disease: eating and swallowing, airway and breathing, infections, health care utilization, cost of care, and behavior. For each subscale, the Tonsil and Adenoid Health Status Instrument demonstrated excellent test-retest reliability (r = 0.72-0.88) and internal consistency reliability (Cronbach alpha = .73-.87). Content validity was ensured during the design process. Construct validity was demonstrated by means of convergent and divergent validity with a global quality-of-life instrument (the Child Health Questionnaire, version PF28). Criterion validity was also satisfactory. Finally, the instrument was appropriately sensitive, with high standardized response means and effect sizes. CONCLUSIONS: The Tonsil and Adenoid Health Status Instrument is a valid, reliable, and sensitive instrument with 6 distinct subscales. This instrument has significant utility for outcomes research in children with tonsil and adenoid disease.

Adenoids↗

PubMed2006

A randomised controlled trial of acupuncture care for persistent low back pain: cost effectiveness analysis.

OBJECTIVE: To evaluate the cost effectiveness of acupuncture in the management of persistent non-specific low back pain. DESIGN: Cost effectiveness analysis of a randomised controlled trial. SETTING: Three private acupuncture clinics and 18 general practices in York, England. PARTICIPANTS: 241 adults aged 18-65 with non-specific low back pain of 4-52 weeks' duration. INTERVENTIONS: Ten individualised acupuncture treatments over three months from acupuncturists trained in traditional Chinese medicine (n = 160) or usual care only (n = 81). MAIN OUTCOME MEASURE: Incremental cost per quality adjusted life year (QALY) gained over two years. RESULTS: Total costs to the United Kingdom's health service during the two year study period were higher on average for the acupuncture group (460 pounds sterling; 673 euros; 859 dollars) than for the usual care group (345 pounds sterling) because of the costs associated with initial treatment. The mean incremental health gain from acupuncture at 12 months was 0.012 QALYs (95% confidence interval -0.033 to 0.058) and at 24 months was 0.027 QALYs (-0.056 to 0.110), leading to a base case estimate of 4241 pounds sterling per QALY gained. This result was robust to sensitivity analysis. The probabilistic sensitivity analysis showed acupuncture to have a more than 90% chance of being cost effective at a pound20 000 cost per QALY threshold. CONCLUSION: A short course of traditional acupuncture for persistent non-specific low back pain in primary care confers a modest health benefit for minor extra cost to the NHS compared with usual care. Acupuncture care for low back pain seems to be cost effective in the longer term. TRIAL REGISTRATION: ISRCTN80764175 [controlled-trials.com].

Acupuncture Therapy↗

PubMed2003

Substantial potential for reductions in coronary heart disease mortality in the UK through changes in risk factor levels.

STUDY OBJECTIVE: The UK government called for a 40% reduction in cardiovascular disease mortality in those aged under 75 by 2010. This paper examines the potential for cardiovascular risk factor changes to reduce coronary heart disease deaths in Scotland, and then extrapolates the findings to the UK population. DESIGN: Secondary analysis of published data using a previously validated mortality model. The model combines uptake and effectiveness of treatments with risk factor trends by sex and age group. It was used to estimate the expected reductions in coronary heart disease mortality: (a) if recent risk factor trends simply continued; (b) if additional risk factor reductions were achieved in line with Scandinavia and the United States. An "analysis of extremes" sensitivity analysis was then carried out. SETTING: Scotland and UK. PARTICIPANTS: Projected Scottish population aged 45+ in 2010 (2.4 million) and UK population of 26.8 million. MAIN RESULTS: Continuation of current trends would result in 2169 fewer coronary deaths in 2010 (minimum estimate 1191 from sensitivity analyses to maximum 3870). About 4749 fewer deaths (minimum 3085, maximum 7155) could be achieved by: (a) a reduction in smoking prevalence from 30% to 18% (about 1668 fewer deaths); (b) a mean population cholesterol reduction from 6.2 to 5.2 mmol/l (about 2167 fewer deaths); (c) a 3.7 mm Hg fall in diastolic blood pressure (about 914 fewer deaths). Extrapolation from the Scottish population to the UK suggests 24 000 fewer deaths in 2010 if current trends continue, or 53 000 fewer deaths with the additional reductions. CONCLUSIONS: With additional interventions it would be possible to almost halve current UK coronary heart disease mortality. Even without gains from medical treatments, the UK government target of 28 000 fewer deaths in 2010 does not seem challenging.

Adult↗

PubMed2001

Interferon and ribavirin for patients with chronic hepatitis C who did not respond to previous interferon therapy: a meta-analysis of controlled and uncontrolled trials.

The efficacy of interferon (IFN) combined with ribavirin for the treatment of patients with hepatitis C who failed to respond to initial IFN therapy is not well established. The primary goal of this study was to perform a systematic review of the literature evaluating the efficacy of combination therapy in nonresponders. Studies were retrieved from MEDLINE, abstracts of scientific meetings, and review of the bibliographies of retrieved studies. Controlled trials were included in the primary analysis whereas uncontrolled trials and trials reported as abstracts were included for sensitivity analysis. The primary endpoints were biochemical and virologic response. A combined estimate of the odds ratio (OR) for each endpoint was obtained by using the random effects model. The number needed to treat (NNT) was calculated by taking the inverse of the pooled risk difference. Nine controlled trials (789 patients) were identified. Six months after treatment, the overall sustained biochemical and virologic responses to 24 weeks of combination therapy were 15.2% and 13.2% with a common OR of 3.8 (95% confidence interval [CI] 2.2-6.7) and 4.9 (95% CI 2.1-11.2) compared with patients treated with IFN monotherapy. The pooled risk difference for the sustained virologic response (SVR) to combination therapy was 7% (95% CI 2-13). The NNT was 14 (95% CI 8-50), suggesting that approximately 14 patients would need to be treated with 6 months of combination therapy for 1 patient to have a SVR. A number of variables were associated with a high response rate in individual studies. Sensitivity analysis of preliminary trials suggest a higher response rate with longer duration of therapy and non-type 1 genotypes.

Adult↗

PubMed2026

A model of cellular proliferation and mitochondrial biogenesis predicts prognosis and immunotherapy response in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD), which is the leading subtype of non-small cell lung cancer (NSCLC), poses considerable difficulties in accurate prognostic assessment and targeted therapeutic options. Cell proliferation-related genes (CPGs) and mitochondrial biogenesis-related genes (MBGs) play critical roles in tumor metabolic reprogramming; however, their prognostic value and molecular mechanisms in LUAD are poorly understood. This study aims to construct a CPG/MBG-based prognostic risk model for LUAD, evaluate its clinical utility in predicting prognosis and immunotherapy response, and experimentally validate the functional role of key model genes in LUAD progression. METHODS: By utilizing The Cancer Genome Atlas (TCGA)-LUAD and GSE72094 datasets, this investigation formulated a risk scoring model through differential expression screening combined with least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. The molecular characteristics and clinical implications of the risk model were investigated via immune microenvironment evaluation, genomic alteration analysis, and drug sensitivity prediction. The functional contributions of key genes were further substantiated using quantitative reverse transcription polymerase chain reaction (qRT-PCR), commercial assay kits, the JC-1 fluorescent probe, the Cell Counting Kit-8 (CCK-8), Transwell invasion assays, and wound healing assays. RESULTS: A risk model based on seven CPGs and MBGs (PLK1, HMMR, CYP27A1, LDHA, NPAS2, KRT17, CIDEC) showed reliable predictive performance in both GSE72094 and the TCGA-LUAD cohorts. Enhanced tumor heterogeneity and an immunosuppressive microenvironment were observed in the high-risk group. Drug sensitivity analysis indicated that the risk model could guide personalized treatment strategies; for instance, high-risk patients showed increased susceptibility to agents such as docetaxel and 5-fluorouracil. In vitro experiments demonstrated that the key gene CIDEC exhibited upregulated expression in LUAD tissues and cells. Knockdown of CIDEC led to enhanced cellular energy metabolism and increased mitochondrial membrane potential, while also effectively suppressing cell invasion, proliferation, and migration. CONCLUSIONS: The established MBGs/CPGs prognostic model provides a novel tool for stratified treatment planning in LUAD, underscoring the crucial roles of cellular proliferation and mitochondrial biogenesis in tumor progression. Functional validation of CIDEC offers experimental support for the development of potential therapeutic strategies.

Lung adenocarcinoma (LUAD)↗

PubMed2006

Performance of antibodies against tissue transglutaminase for the diagnosis of celiac disease: meta-analysis.

A meta-analysis of studies investigating the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) for antibodies against tissue transglutaminases (tTG) of various origins in celiac disease (CD) diagnosis was carried out. Twenty-one studies, with untreated CD patients and healthy/CD-free controls, were included in the meta-analysis. The diagnostic accuracy was estimated using a summary receiver operating characteristic (SROC) curve and pooled sensitivity (Se) and specificity (Sp). Multiple assays within a study were treated by considering all the assays within a study and by analyzing the most popular assay (i.e., the commercial anti-tTTG ELISA most frequently utilized in the papers in which multiple assays were included). The SROC curve indicated the absence of heterogeneity, and the superiority of recombinant human tTG (rh-tTG) and purified human tTG (ph-tTG) compared to guinea pig-tTG (gp-tTG). The sensitivities (most popular assay) for rh-tTG, ph-tTG, and gp-tTG were 94%, 90%, and 92%, respectively, and the specificities were 97%, 92%, and 96%, respectively. A sensitivity analysis (exclusion of studies with bias) altered the results of ph-tTG: Se, 95%; Sp, 98%. The sensitivities (all individual assays) for rh-tTG, ph-tTG, and gp-tTG were 94%, 94%, and 91%, respectively, and the specificities were 95%, 94%, and 89%, respectively. Human tTG ELISA is sensitive and specific, and it can be used for mass screening. Sensitivity analysis showed that ph-tTG might perform better.

Animals↗

PubMed1989

Screening vs. individual detection of industrial fluorosis: a decision analysis model.

In preventive medicine and occupational health, decision-makers face uncertainty, divergent opinions, and varying needs. In the Swiss aluminum industry, screening for industrial fluorosis illustrates how decision analysis and cost-effectiveness analysis can provide rational and explicit models of decision-making in such contexts. Data on fluoride-exposed potroom workers are used to compare the cost-effectiveness of two strategies: mass screening of fluorosis versus individual detection of the disease on the basis of the worker's symptoms. A decision-analysis and a sensitivity analysis are performed to assess the impact of the screening program for different levels of expected prevalence of the disease. The optimal decision, in economic terms, is the one that minimizes the pension and screening-related costs and maximizes the number of years of full working capacity. Swiss data suggest that a diagnosis of clinical fluorosis is unlikely before 10 years of exposure to fluoride. Between 10 and 30 years of exposure to fluoride, mass screening may be more cost-effective than individual detection of the disease, even when the expected prevalence of the disease in a given industrial setting is less than 10%.

Aluminum↗

PubMed2003

Bayesian approaches to multiple sources of evidence and uncertainty in complex cost-effectiveness modelling.

Increasingly complex models are being used to evaluate the cost-effectiveness of medical interventions. We describe the multiple sources of uncertainty that are relevant to such models, and their relation to either probabilistic or deterministic sensitivity analysis. A Bayesian approach appears natural in this context. We explore how sensitivity analysis to patient heterogeneity and parameter uncertainty can be simultaneously investigated, and illustrate the necessary computation when expected costs and benefits can be calculated in closed form, such as in discrete-time discrete-state Markov models. Information about parameters can either be expressed as a prior distribution, or derived as a posterior distribution given a generalized synthesis of available data in which multiple sources of evidence can be differentially weighted according to their assumed quality. The resulting joint posterior distributions on costs and benefits can then provide inferences on incremental cost-effectiveness, best presented as posterior distributions over net-benefit and cost-effectiveness acceptability curves. These ideas are illustrated with a detailed running example concerning the cost-effectiveness of hip prostheses in different age-sex subgroups. All computations are carried out using freely available software for conducting Markov chain Monte Carlo analysis.

Adult↗

PubMed2005

Cost comparison of anterior cruciate ligament reconstruction: autograft versus allograft.

PURPOSE: To compare the economic costs associated with anterior cruciate ligament (ACL) reconstruction using either autograft or allograft. The surgical costs are reported, including charge categories, for each procedure. All operations were performed in the Southern United States of America. TYPE OF STUDY: Evaluation of cost data collected from a group of patients participating in a prospective, nonrandomized trial. METHODS: A total of 122 patients with ACL-deficient knees undergoing surgical reconstruction using either bone-patellar tendon-bone autograft (n = 86) or freeze-dried Achilles tendon allograft (n = 37) were analyzed (1 patient underwent 2 allograft reconstructions). Patient selection for groups was based on the physician performing the surgery (2 surgeons performed autografts and 1 performed allografts). Groups were compared with respect to age, sex, race, and occupation. Hospital charge data were retrieved from the billing department and divided into various categories for comparison of the 2 groups. RESULTS: The mean hospital charge for ACL reconstruction was 4,622 dollars for allograft and 5,694 dollars for autograft (P < .0001). Differences included increased operating room time and a greater likelihood of overnight hospitalization for autograft procedures. This was slightly offset by higher charges for operating room supplies for allograft reconstructions owing to the cost of the graft itself. CONCLUSIONS: Allograft reconstruction of the ACL was significantly less expensive than autograft bone-patellar tendon-bone reconstruction. Allograft ACL reconstruction is a less costly alternative to autograft reconstruction. LEVEL OF EVIDENCE: Level IV, economic analysis with no sensitivity analysis.

Adult↗

PubMed2005

Optimal experiment design for cardinal values estimation: guidelines for data collection.

Optimal experiment design for parameter estimation (OED/PE) is an interesting technique for modelling practices when aiming for maximum parameter estimation accuracy. Nowadays, experimental designs for secondary modelling within the field of predictive microbiology are mostly arbitrary or based on factorial design. The latter type of design is common practice in response surface modelling approaches. A number of levels of the factor(s) under study are selected and all possible treatment combinations are performed. It is however not always clear which levels and treatment combinations are most relevant. An answer to this question can be obtained from optimal experiment design for-in this particular case-parameter estimation. This technique is based on the extremisation of a scalar function of the Fisher information matrix. The type of scalar function determines the final focus of the optimised design. In this paper, optimal experiment designs are computed for the cardinal temperature model with inflection point (CTMI) and the cardinal pH model (CPM). A model output sensitivity analysis (depicting the sensitivity of the model output to a small change in the model parameters) yields a first indication of relevant temperature or pH treatments. Performed designs are: D-optimal design aiming for a maximum global parameter estimation accuracy (by minimising the determinant of the Fisher information matrix), and E-optimal design improving the confidence in the most uncertain model parameter (by maximising the smallest eigenvalue of the Fisher information matrix). Although lowering the information content of a set of experiments, boundary values on the design region need to be imposed during optimisation to exclude unworkable experiments and partly account for incorrect nominal parameter values. Opposed to the frequently applied equidistant or arbitrary treatment placement, optimal design results show that typically four informative temperature or pH levels are selected and replicate experiments are to be performed at these points. Informative experiments are typically placed at points with an extreme model output sensitivity.

Bacteria↗

PubMed2005

Mathematical models of the fate of lymphoma B cells after antigen receptor ligation with specific antibodies.

We formulate models of the mechanism(s) by which B cell lymphoma cells stimulated with an antibody specific to the B cell receptor (IgM) become quiescent or apoptotic. In particular, we aim to reproduce experimental results by Marches et al. according to which the fate of the targeted cells (Daudi) depends on the levels of expression of p21(Waf1) (p21) cell-cycle inhibitor. A simple model is formulated in which the basic ingredients are p21 and caspase activity, and their mutual inhibition. We show that this model does not reproduce the experimental results and that further refinement is needed. A second model successfully reproduces the experimental observations, for a given set of parameter values, indicating a critical role for Myc in the fate decision process. We use bifurcation analysis and objective sensitivity analysis to assess the robustness of our results. Importantly, this analysis yields experimentally testable predictions on the role of Myc, which could have therapeutic implications.

Apoptosis↗

PubMed2003

Cost-effectiveness analysis of inhaled corticosteroids in asthma: a review of the analytical standards.

PURPOSE: To determine whether published cost-effectiveness studies on inhaled corticosteroids (ICS) in asthma adhered to basic analytical standards as defined in health economic textbooks and in guidelines assessing and comparing efficacy and safety. METHODS: Original cost-effectiveness studies published between 1990 and 2000 in general medical or economic journals were reviewed to assess the adherence to five fundamental methodological principles: (1) design of the study, (2) choice of perspective and corresponding costs, (3) choice of outcome measure, (4) marginal cost analysis, and (5) sensitivity analysis and discussion about external validity. For each principle, the studies were ranked as high, medium or low quality. RESULTS: Most of the 18 studies included were ranked medium on the first two principles. The studies adhered to a higher degree to the remaining three principles. Only three studies were high ranked in all five principles. The number of principles fulfilled increased over time. Studies comparing pharmaceutical products from competing companies were typically short-term studies, designed for other purposes than health economic analyses, and, in general, did not use therapeutically equivalent dosing. CONCLUSIONS: Attention should be drawn to the study design, the weak correspondence between perspective and costs, and especially to the impact of bias in health economic results when comparing different doses of ICSs.

Administration, Inhalation↗

PubMed2025

Association among blood pressure, antihypertensive drugs, and amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease. The impacts of antihypertensive drugs and blood pressure (BP) on ALS are currently debatable. OBJECTIVE: To evaluate the causal relationship involving antihypertensive drugs, BP, and ALS through a Mendelian randomization (MR) analysis. METHODS: The causal relationship between BP and ALS was evaluated by a bidirectional two-sample MR analysis. Then, a sensitivity analysis was performed using a secondary BP genome-wide association study. The drug-target MR was employed to evaluate the impact of antihypertensive drugs on ALS. Furthermore, we used cis-expression quantitative trait loci (cis-eQTLs) data from brain tissue and blood to validate the positive results by a summary-based MR method. RESULTS: We found that an increment in systolic BP (SBP) could elevate the risk of ALS (inverse-variance weighted [IVW] odds ratio [OR] = 1.003; 95% confidence interval [95%CI]: 1.001-1.006; per 10-mmHg increment) and ALS might be protected by angiotensin-converting enzyme inhibitors (ACEIs; OR = 0.970; 95%CI: 0.956-0.984; p = 1.96 × 10-5; per 10-mmHg decrement). A causal relationship was not observed between diastolic BP and other antihypertensive drugs in ALS. CONCLUSION: In the present study, genetic support for elevated SBP serves as a risk factor for ALS. Besides, ACEIs hold promise as a candidate for ALS.

Humans↗