Evaluating and Valuing Drugs for Rare Conditions: No Easy Answers

We find ourselves in an era of unprecedented growth in the development and use of so-called “orphan” drugs to treat rare diseases, which are poised to represent more than one-fifth of pharmaceutical expenditures by 2022. This widespread use has been facilitated by legislative and regulatory incentives in both the United States and abroad, yet US payers and health systems have not yet made a concerted effort to understand whether and how rare diseases require special considerations on their part and how to adapt traditional methods of health technology assessment and economic evaluation to accommodate these situations. In this article, we explore the general ethical dilemmas that rare diseases present, steps taken by health technology assessment bodies worldwide to define the level of rarity that would necessitate special measures and the modifications to their assessment and valuation processes needed, and the contextual components for rare-disease evaluation that lie outside of the assessment framework as a guide to US decision makers on constructing a formal and relevant process stateside.     

The effect of Nd:YAG pulse duration on dentine crater depth

OBJECTIVES: The effect of alteration of laser parameters on laser-dentine interaction, in particular the effect of pulse duration, has not been well documented. The aim of this in vitro study was to determine the effect on dentine crater depth of Nd:YAG laser pulse duration, and total delivered energy, dentine site and the presence or absence of dye. METHODS: Ninety-six sound third molars were extracted and sectioned transversely to provide 192 upper and lower cut surfaces. The upper surfaces were painted with a layer of dye (IR5) suitable for absorption at 1064 nm. The specimens were divided into 16 sub-groups and exposed to two Nd:YAG lasers; one of pulse duration 7 ms and the second of pulse duration 35 ps. Both lasers operated in a non-contact mode (spot diameter 165 microm) with repetition rates of 10.5 and 10 Hz, respectively. Four total energies (2.28, 2.64, 3.6, 4.2 J) were delivered to eight dyed and eight undyed sub-groups. Eight outer and five inner sites were irradiated on each specimen. Dentine crater depth was measured five times using a Reflex Microscope and a three-dimensional centre of gravity derived. An upper and lower specimen were taken from each sub-group and viewed under a SEM. RESULTS: ANOVA and multiple regression analysis were applied and the following factors were found to have a statistically significant effect on crater depth (p<0.0001): total delivered energy, pulse duration and inner/outer location. CONCLUSIONS: Increasing energy and pulse duration produced deeper craters. Similarly inner dentine sites produced deeper crater depths. Only craters produced at the ms pulse duration were carbonised. It would appear that laser-dentine interaction has a non-thermal component at picosecond pulse duration.     

Torsional testing of Canal Master U hand instruments.

Ten each of size 25, 30, 35, 40, and 45 Canal Master U hand instruments were tested for torsional failure and revolutions to failure. In addition, the point at which separation occurred was measured on the instrument shaft. An Instron 1125 machine was used for all torsion testing. The mean torque failure value for size 25 and 35 Canal Master U instruments exceeded the ADA specification No. 28 minimum values while sizes 30, 40, and 45 were below the ADA minimum average values. All Canal Master U averages for revolutions to failure exceeded the ADA minimums. Although size 25 was above the minimum average, due to a wide range of values, 5 of the 10 were below the ADA specification No. 28 values. The point of instrument separation was 0.325 to 1.575 mm behind the cutting head. Due to the structural design differences of endodontic files versus Canal Master U, it is suggested that an additional category of ADA specification be introduced for Canal Master endodontic instruments.     

Arterial embolisation of a facial haemangioma.

Non-invasive investigations in the diagnosis of highly vascular lesions are without doubt a sound principle. A case is presented however, in which the clinical diagnosis of a haemangioma was confirmed by ultrasound and magnetic resonance imaging (MRI) but required further investigation by angiography to facilitate treatment. Embolisation is a well established technique available in most large radiology departments, but may not be well known by general dental practitioners.     

Testing the applicability of a conceptual model of oral health in housebound edentulous older people

Abstract – Objectives: The aim of the study was to test prospectively Wilson and Cleary’s ( 1 ) conceptual model of the direct and mediated pathways between symptom burden, functional status and health perceptions in relation to the oral health of housebound elderly edentulous people. Methods: The data were collected as part of a community based randomized control trial of a domiciliary denture service for older people. Measures of self‐reported symptoms, functional status and global oral and general health perceptions were collected from 133 participants prior to treatment and at 3‐month follow‐up. Results: The results indicated support for the dominant direct and indirect pathways within the model; worse patient reported symptoms predicted a lower functional status; worse daily functioning predicted lower global oral health perceptions. In addition, the impact of symptom status on oral health perceptions was mediated by patient reported functioning. The treatment (domiciliary denture service) significantly improved functional status and global oral health perceptions. All relationships were significant prospectively that is, from baseline, prior to the intervention, to 3‐month follow‐up, with the exception of between symptoms functioning. Conclusion: The results support Wilson and Cleary’s conceptual model of patient outcomes as applied to elderly edentulous people. They highlight the importance of assessing a range of patient‐orientated variables in order to help gain a greater understanding of how oral health impacts on individuals’ daily lives and well‐being. Further conceptual development of the model is discussed, particularly the role of individual difference factors.     

Effectiveness of nurse-led brief alcohol intervention: a cluster randomized controlled trial

AIM: This paper reports an evaluation of the effectiveness and cost-effectiveness of nurse-led screening and brief intervention in reducing excessive alcohol consumption among patients in primary health care. BACKGROUND: Excessive alcohol consumption is a major source of social, economic and health problems. However, such consumption is responsive to brief alcohol intervention. To date, brief intervention research in primary health care has focused on general practitioner-led interventions, and there is only circumstantial evidence of effectiveness in nurse-led interventions. However, nurses are increasingly taking a lead in health promotion work in primary care. METHODS: A pragmatic cluster-randomized controlled trial was carried out between August 2000 and June 2003 to evaluate the effects of a brief intervention compared with standard advice (control condition). A total of 40 general practice clusters (intervention = 21 and control = 19) recruited 127 patients (intervention = 67 and control = 60) to the trial. Excessive consumption was identified opportunistically via the Alcohol Use Disorders Identification Test. After baseline assessment, patients received either a 5-10 minutes brief intervention using the 'Drink-Less' protocol or standard advice (control condition). Follow-up occurred at 6 and 12 months postintervention. RESULTS: Analysis of variance weighted for cluster size revealed no statistically significant differences between intervention and control patients at follow up. A majority of patients in both conditions reduced their alcohol consumption between assessment and subsequent measurement. Economic analysis suggested that the brief intervention led to no statistically significant changes in subsequent health service resource use relative to standard treatment. CONCLUSION: The brief intervention evaluated in this trial had no effect over standard advice delivered by nurses in primary health care. However, there was a reduction in excessive drinking across both arms of the trial over time. Due to nurse drop-out, this trial was significantly underpowered. Future research should explore barriers to nurses' involvement in research trials, particularly with an alcohol focus. A larger trial is required to evaluate the effectiveness of nurse-led screening and brief alcohol intervention in primary care.