Highlights from Faraday Discussion on Ultrafast Photoinduced Energy and Charge Transfer, Ventura, CA, USA, April 2019.

Following a tradition more than 100 years old, a Faraday Discussion meeting was held on the topic of 'Ultrafast Energy and Charge Transfer' in April 2019. While these meetings are historically held in the United Kingdom, the Royal Society of Chemistry (who organises the conference and publishes its proceedings) recognises the importance of finding the space and opportunity for the chemical sciences international communities to connect and exchange knowledge. As such, the meeting hereby referred to took place in Ventura, California, USA. This conference report, produced by early career researchers, covers the highlights of this meeting, focusing on brief summaries of the papers discussed as well as particularly interesting or recurring topics of the ensuing discussion.

Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial.

BACKGROUND: Etanercept, a soluble tumour necrosis factor receptor, lessens the severity of psoriasis as measured by physician-reported clinical outcomes. Equally important is the patient perspective on the effect of etanercept therapy on daily life. OBJECTIVES: To assess patient-reported outcomes (PROs) in patients with psoriasis receiving etanercept therapy. METHODS: In this multinational, randomized, phase III trial, patients with psoriasis received placebo (n = 193), etanercept 50 mg per week (n = 196) or etanercept 50 mg twice weekly (n = 194) during the initial 12-week, double-blind period. Thereafter, all patients received open-label etanercept (50 mg per week). The following PROs were assessed: Dermatology Life Quality Index (DLQI), Short Form-36 Health Survey (SF-36), patient rating of pruritus, and patient global assessment of psoriasis. RESULTS: At week 12, DLQI total score improved by 65-70% in patients receiving etanercept compared with 6% in patients receiving placebo (P < 0.0001), and improvement in DLQI was clinically meaningful (> or = 5-point improvement or 0 score) for 72-77% of patients receiving etanercept therapy. All DLQI and SF-36 subscales and the SF-36 physical and mental component summary scores demonstrated significantly greater improvement with etanercept therapy than with placebo, illustrating that etanercept benefits patients with psoriasis across multiple domains that contribute to health-related quality of life. With etanercept therapy, distributions of patient ratings of pruritus and global assessment of disease shifted from moderate to severe (baseline) to minimal to good (week 12). Etanercept-induced benefits of PROs were maintained for patients who reduced their dose after 12 weeks. CONCLUSIONS: Etanercept therapy improves PROs in patients with psoriasis and makes a meaningful difference to their lives. These results support the efficacy profile of physician-reported clinical measures while providing a more complete understanding of the benefits experienced by patients with psoriasis treated with etanercept.

Imputing physical health status scores missing owing to mortality: results of a simulation comparing multiple techniques.

BACKGROUND: Having missing data complicates the statistical analysis of health-related quality-of-life (HRQOL) data and, depending on the extent and nature of missing data, can introduce significant bias in treatment comparisons. OBJECTIVE: We evaluated the bias associated with 4 different imputation methods for estimating physical health status (PHS) scores missing as a result of mortality. METHODS: A simulation study was conducted in which we systematically varied mortality rates from 0% to 30% and change in PHS scores from -20 to 20 on a 100-point scale for a 2-group clinical trial with follow-up over 18 months. The 4 imputation methods were last value carried forward (LVCF), arbitrary substitution (ARBSUB), empirical Bayes (BAYES), and within-subject modeling (WSMOD). Pseudo-root mean square residuals (RMSRs) and differences between true and estimated slopes were used to evaluate how well the imputation methods reproduced the true characteristics of the simulated population data. RESULTS: ARBSUB and BAYES methods have the smallest RMSRs compared with LVCF and WSMOD across all mortality rates. As the rate of missing data resulting from mortality increased, all imputation techniques deviated more from population data. The BAYES technique was best at reproducing group slopes in cases with differential mortality rates or when mortality rates exceeded 15%. WSMOD and LVCF significantly underestimated changes in PHS. CONCLUSIONS: The different imputation methods produced comparable results when there were few missing data. The BAYES approach most closely estimated true population differences and change in PHS regardless of missing data rates. These findings are limited to physical health and functioning measures.

Outcomes research in chronic viral hepatitis C: effects of interferon therapy.

Although chronic hepatitis C (CHC) is often mild and asymptomatic, it may lead to decompensated hepatic cirrhosis and death. CHC is now the single most important indication for liver transplantation in North America. CHC is also an important cause of morbidity. Recent work is reviewed and shows that the health-related quality of life (HRQOL) of patients with CHC is markedly reduced compared with that of age- and sex-matched controls. For as yet unknown reasons, this reduction is more severe in CHC patients than in those with chronic hepatitis B. Successful therapy of CHC with type 1 interferons (IFNs) leads to substantial improvement - to nearly normal levels - in patients' HRQOL. In addition, IFN or IFN plus ribavirin therapy for CHC is highly cost effective, despite its limited long term efficacy; estimates of the costs to gain one year of quality-adjusted life range from no cost (that is, therapy is cost saving) to US$11,400 (for those most difficult to cure). Thus, despite the limited effectiveness of current therapies for CHC, they are fully justified based on their beneficial effects on patients' HRQOL and their cost effectiveness.

The concept of clinically meaningful difference in health-related quality-of-life research. How meaningful is it?

It is generally believed that small differences in health-related quality of life (HR-QOL) may be statistically significant yet clinically unimportant. The concept of the minimal clinically meaningful difference (MCID) has been proposed to refer to the smallest difference in a HR-QOL score that is considered to be worthwhile or clinically important. However, there is danger in oversimplification in asking the question: what is the MCID on this HR-QOL instrument? We argue that the attempt to define a single MCID is problematic for a number of reasons and recommend caution in the search for the MCID holy grail. Specifically, absolute thresholds are suspect because they ignore the cost or resources required to produce a change in HR-QOL. In addition, there are several practical problems in estimating the MCID, including: (i) the estimated magnitude varies depending on the distributional index and the external standard or anchor; (ii) the amount of change might depend on the direction of change; and (iii) the meaning of change depends on where you start (baseline value).

Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy. The Consensus Interferon Study Group.

The natural history, prognosis, and clinical significance of chronic hepatitis C are highly variable and somewhat controversial. The purpose of this study was to evaluate the effect of chronic hepatitis C infection on patients' perceptions of health-related quality of life (HRQOL) and to evaluate whether treatment with interferon improves HRQOL. A total of 642 patients with compensated liver disease who were enrolled in a multicenter trial of interferon therapy for chronic hepatitis C had evaluation of HRQOL using the SF-36 and other instruments derived from the Medical Outcomes Study (MOS). These instruments were self-administered by patients at baseline and at the end of a 24-week post-treatment observation period after 24 weeks of interferon treatment. Patients with chronic hepatitis C were compared with healthy controls (n = 750) selected from a representative sample of adults in the United States. Unadjusted and age/gender-adjusted results were similar, as were analyses using parametric or nonparametric methods. Compared with healthy controls, patients with chronic hepatitis C at baseline had lower HRQOL on all eight scales of the SF-36 (P <.001 for all). Patients without cirrhosis (n = 284 ) showed similar although slightly smaller differences. The differences were highly significant, clinically and socially relevant, and greatest for those scales that were more reflective of physical than mental or emotional disease. Patients who had a sustained viral response to interferon therapy (n = 41) exhibited marked improvements in HRQOL, and these improvements exceeded those of nonresponders on 13 of 14 HRQOL scales (8 were statistically significant). Similar improvements were noted in patients with sustained biochemical responses. The authors concluded that patients with chronic hepatitis C with or without cirrhosis have markedly reduced HRQOL. Patients who had a sustained response (virological or biochemical) to interferon therapy experienced significant improvements in perceived wellness and functional status. Successful interferon therapy provides meaningful improvements in HRQOL in patients with chronic hepatitis C.

Consumer information, price, and nonprice competition among hospitals.

The results of the empirical analysis in this paper indicate that broadly defined hospital quality declines in more concentrated markets. The direction of the effect of concentration on hospital charges is smaller and the direction is less clear. Prices are little, if any, lower in more concentrated markets. Hospital price-cost margins are higher in more concentrated markets. Higher concentration discourages price competition. The data do not support the increasing monopoly theory. Further, since hospital price-cost margins do not appear to remain constant, we must reject the redundant resources theory as well, though its stress on nonprice competition rings true. The empirical results are consistent with the traditional antitrust theory. In addition, consumer information plays a surprisingly important role. Consumer information is important in explaining hospital prices, and less important in hospital quality. Consumers are not passive; they do play a role in hospital choice. It is likely that more recent innovations in health insurance will increase consumer awareness. With an increase in consumer copayments, and more active insurer contracting, it is likely that future hospital competition is more likely to stress price, and future antitrust activity could lead to price reductions in addition to declining hospital price-cost margins.

The competitive effects of horizontal mergers in the hospital industry.

Past empirical research has associated higher prices (and potentially profits) with less concentrated hospital markets. This has led to consternation among policymakers who must decide whether or not to apply traditional antitrust guidelines to hospital mergers. Due to the inherent flaws of accounting data, an 'event study' methodology is used to examine the effects of merger related announcements on the competitors' stock price returns. The results provide evidence that events which promote mergers increase the profits of competitors, while events which deter mergers decrease them. Furthermore, the greater the merger impact on local hospital markets, the stronger the effect.

Changing oral hygiene attitudes and habits.

Up to the time of establishment (1962) of the Dental Health Education and Research Foundation, the philosophy and practice of preventive dentistry was almost unknown in Australia. Australians' dental health was generally as bad as any country in the world. Children were given little dental health instruction in schools. The majority of parents were seemingly uninformed about the need for the preservation and care of their own or their children's teeth. Dental Health Educators were trained to instruct school children in such subjects as diet, oral hygiene and plaque control. A Good Teeth Puppet Theatre was established and a special preventive dentistry orientated script written. A Mobile Dental Health Education Unit (caravan), equipped with a room darkened and lit by ultraviolet light, audiovisual instruction area and a mini laboratory, was built and set up in secondary schools. Pupils are encouraged to have their plaque disclosed using a yellow dye which becomes fluorescent when viewed under ultraviolet light; descriptive films are demonstrated and personal dental health instruction given. More than two and a half million children have participated in these programs. Evaluation studies of the school programs revealed that after six months children were able to recall more than 70% of the dental health message. Results of a recent WHO survey of the oral health status of 13-14-year-olds in Canterbury (New Zealand), Sydney (Australia), Trondelag (Norway), Yamanashi (Japan) and Hannover (West Germany) showed that the Sydney children had the lowest caries rate. The Sydney survey was carried out in the same are where the above Dental Health Education and Research Foundation community dental health programs operate.