37 research outputs found
Are decisions using cost-utility analyses robust to choice of SF-36/SF-12 preference-based algorithm?
BACKGROUND: Cost utility analysis (CUA) using SF-36/SF-12 data has been facilitated by the development of several preference-based algorithms. The purpose of this study was to illustrate how decision-making could be affected by the choice of preference-based algorithms for the SF-36 and SF-12, and provide some guidance on selecting an appropriate algorithm. METHODS: Two sets of data were used: (1) a clinical trial of adult asthma patients; and (2) a longitudinal study of post-stroke patients. Incremental costs were assumed to be /QALY), were ranked and compared between datasets. RESULTS: In the asthma patients, estimated ICURs ranged from Lawrence's SF-12 algorithm at 63,492/QALY (95% CI: 48,780 to 83,333). ICURs for the stroke cohort varied slightly more dramatically. The MEPS-based algorithm by Franks et al. provided the lowest ICUR at 50,000/QALY and did not have confidence intervals that overlapped with most of the other algorithms. The ICUR-based ranking of algorithms was strongly correlated between the asthma and stroke datasets (r = 0.60). CONCLUSION: SF-36/SF-12 preference-based algorithms produced a wide range of ICURs that could potentially lead to different reimbursement decisions. Brazier's SF-36 and SF-12 algorithms have a strong methodological and theoretical basis and tended to generate relatively higher ICUR estimates, considerations that support a preference for these algorithms over the alternatives. The "second-generation" algorithms developed from scores mapped from other indirect preference-based measures tended to generate lower ICURs that would promote greater adoption of new technology. There remains a need for an SF-36/SF-12 preference-based algorithm based on the US general population that has strong theoretical and methodological foundations
A Prescription for Improving Drug Formulary Decision Making
Gordon Schiff and colleagues present a new tool and checklist to help formularies make decisions about drug inclusion and to guide rational drug use
Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?
Research into the mechanisms by which proteins fold into their native structures has been on-going since the work of Anfinsen in the 1960s. Since that time, the folding mechanisms of small, water-soluble proteins have been well characterised. By contrast, progress in understanding the biogenesis and folding mechanisms of integral membrane proteins has lagged significantly because of the need to create a membrane mimetic environment for folding studies in vitro and the difficulties in finding suitable conditions in which reversible folding can be achieved. Improved knowledge of the factors that promote membrane protein folding and disfavour aggregation now allows studies of folding into lipid bilayers in vitro to be performed. Consequently, mechanistic details and structural information about membrane protein folding are now emerging at an ever increasing pace. Using the panoply of methods developed for studies of the folding of water-soluble proteins. This review summarises current knowledge of the mechanisms of outer membrane protein biogenesis and folding into lipid bilayers in vivo and in vitro and discusses the experimental techniques utilised to gain this information. The emerging knowledge is beginning to allow comparisons to be made between the folding of membrane proteins with current understanding of the mechanisms of folding of water-soluble proteins
Outer membrane protein folding from an energy landscape perspective
The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OFMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding
Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research
Is It a Good Time to Be a Pharmacist in the US?
The labor market for pharmacists in the United States has seen significant dynamics over the past couple of decades in both demand and supply. The purpose of this brief editorial is to discuss some key concerns for pharmacists in the current labor market and over the next decade. A key issue in evaluating how pharmacists will fare in moving forward into expanded clinical roles and functions will be the degree to which they expand their professional autonomy
Is It a Good Time to Be a Pharmacist in the US?
The labor market for pharmacists in the United States has seen significant dynamics over the past couple of decades in both demand and supply. The purpose of this brief editorial is to discuss some key concerns for pharmacists in the current labor market and over the next decade. A key issue in evaluating how pharmacists will fare in moving forward into expanded clinical roles and functions will be the degree to which they expand their professional autonomy
Cost and Effectiveness Analysis of Rate versus Rhythm Control of Atrial Fibrillation in Patients with Heart Failure
Background. Coexistence of atrial fibrillation (AF) and heart failure (HF) has been shown to produce a worse prognosis than either condition alone. Rate and rhythm control are two common treatment options in the management of AF; however, the relative cost effectiveness of these options in this population is not known. Objective. To compare costs and health outcomes in rate versus rhythm control of AF in HF. Methods. A Markov model was created to calculate all the costs and effects of rate and rhythm control strategies. The simulation cohort starting age was 65 with a diagnosis of AF and HF. Costs were measured in 2008 US dollars and clinical outcomes in quality-adjusted life-years, taking the third-party payer perspective. Economic outcomes of interest were drug acquisition, AF and HF hospitalization, and severe side effect costs. Costs and transition probabilities were obtained from the most rigorous studies available (pre-defined criteria) identified in MEDLINE and EMBASE searches and references of published manuscripts. Inpatient costs were obtained from the Healthcare Cost and Utilization Project database. A probabilistic sensitivity analysis was also conducted. Results. In the base-case analysis, the incremental life expectancy per patient of rhythm versus rate control as initial treatment was -0.154 quality-adjusted life years (2.827 versus 2.982), while the incremental life time cost was 29,589 versus $22,669 per patient per year). The same results were observed in the probabilistic sensitivity analysis. Conclusion. Based on this cost-effectiveness analysis, rate control should be the initial treatment of AF in this population. Grant. Not funded
Comparison of Rate Control versus Rhythm Control for Management of Atrial Fibrillation in Patients with Coexisting Heart Failure: A Cost-Effectiveness Analysis
STUDY OBJECTIVE: To compare lifetime costs and health outcomes of rate control versus rhythm control for management of atrial fibrillation in patients with coexisting heart failure from the third-party payer perspective.
DESIGN: A Markov decision analysis model constructed from costs, utility, and transition probability inputs obtained from randomized clinical trials and publically available databases.
PATIENTS: A simulated cohort aged 65 years or older with persistent or paroxysmal atrial fibrillation and heart failure.
MEASUREMENTS AND MAIN RESULTS: Markov states for rhythm control were cardioversion plus amiodarone and maintenance amiodarone, and those for rate control were β-blocker, digoxin, and calcium channel blocker. Transition states included treatment success, hospitalizations for atrial fibrillation and/or heart failure, and severe adverse effects. Economic inputs included cost for drugs, cost of hospitalizations for atrial fibrillation and/or heart failure, and cost of management of severe adverse effects. Costs were measured in 2009 U.S. dollars, and clinical outcomes in quality-adjusted life-years (QALYs). One-way and multivariable sensitivity analyses were conducted. Uncertainty intervals (UIs) were obtained from probabilistic sensitivity analyses. Rate control was found to be less costly and more effective than rhythm control. Base case and probabilistic sensitivity analyses cost and effectiveness values for rate control were 5517-9016) and 2.395 QALYs (95% UI 2.366-2.424 QALYs); whereas those for rhythm control were 11,033-21,434) and 2.197 QALYs (95% UI 2.155-2.237 QALYs). No critical values were found for any model parameters in the one-way sensitivity analyses. The cost-effectiveness acceptability curves showed that rate control was considered cost-effective in 100% of cases at willingness-to-pay ratios between 200,000/QALY.
CONCLUSION: Rate control is less costly and more effective than rhythm control and should be the initial treatment for atrial fibrillation among patients with coexisting heart failure