Pharmacists are initiators in palliative care for patients with rare diseases.

The World Health Organization supports early delivery of palliative care as it reduces unnecessary hospital admissions and the inappropriate use of health care services. A community pharmacist can play a key role in advocating timely access to palliative care. Medication reconciliation must alert them to start communicating with the patient and/or his relatives about refocusing treatment and care as part of palliative and terminal care. Pharmaceutical activities for these patients include dispensing of devices and medicinal products, compounding personalized medication and participating as a member of the Palliative Support Team. Most of the several thousands of rare diseases are caused by genetic defects and up to now have no cure and a late diagnosis.

Orphan medical devices have come a long way.

BACKGROUND: In many countries worldwide orphan drug regulations are installed but only the United States of America and Japan have an orphan device regulation. For many years surgeons have used off-label or self-assembled medical devices for the prevention, diagnosis or treatment of rare disorders. Four examples are given: an external cardiac pacemaker, a metal brace for clubfoot in newborns, a transcutaneous nerve stimulator and a cystic fibrosis mist tent. CONCLUSION: In this article we argue that we need authorized medical devices as well as medicinal products to prevent, diagnose and treat patients with life-threatening or chronically debilitating disorders with a low prevalence/incidence. Several arguments are given to support this statement.

Characteristics of Early Phase Clinical Trials for Rare Cancers: Insights From Interviews With Stakeholders.

Background: Rare cancers occur with an incidence of no more than six cases per 100,000 people according to the definition used by the Surveillance of Rare Cancers in Europe project. For a variety of reasons (low prevalence, cytotoxicity), it is challenging to perform the necessary clinical studies to investigate the safety and efficacy of investigational medicines against such rare malignancies, reformulating even at the earliest stages of the drug development process. This article investigates the differences between phase I rare cancer trials performed in commercial (companies) and non-commercial settings (academic hospitals). Materials and Methods: The differences were explored through the conduct of semi-structured interviews with three different stakeholder groups: representatives from academia (n = 7), representatives from companies (n = 4) and representatives from patient organizations (n = 4). All the interviews were transcribed verbatim and analyzed in NVivo using the framework method. Results: According to the interviewees, the academic and commercial stakeholders collaborate in the majority of phase I rare cancer trials. In general, the commercial partner finances the trial, whereas academia is responsible for the execution of the study procedures. The average cost of undertaking these trials is difficult to estimate because it depends on what is specifically requested during the trial. The 3 + 3 study design remains the most widely used design and the use of expansion cohorts is controversial. With regard to the regulatory aspects of phase I rare cancer trials, it was expressed that a good regulatory framework facilitates the conduct of these studies, but that increased regulation and oversight also has drawbacks, e.g., differences in standards between different ethics committees, over interpretation of the rules, insufficient availability of qualified personnel and higher workloads. The patient organization representatives claimed that patients experience no differences in terms of accommodation, compensation and paperwork between the academic and commercial settings or the degree of follow-up. They also believed that the direct input of patients can bring added value to such studies not only with regard to the recruitment process and the feasibility of the study but also the legibility of the informed consent forms. Conclusion: The growing need for first-in-man trials in rare malignancies needs to be highlighted, as difficult as they are to undertake and to co-develop, not only because rare cancer patients deserve an appropriate treatment, but also because these medicines represent the future of cancer therapy in the precision medicine era. Cooperation of commercial and academic sites are needed. Patient organizations need to be educated to take part in this process.

The hydrolytic stage in high solids temperature phased anaerobic digestion improves the downstream methane production rate.

The role of the hydrolytic stage in high solids temperature phased anaerobic digestion was investigated with a mixture of cattle slurry and maize silage with variable ratios (100, 70 and 30% volatile solids coming from cattle slurry). It was incubated for 48 h at 37, 55, 65 and 72 °C. Soluble chemical oxygen demand and biochemical methane potential were measured at 0, 24 and 48 h. Higher temperatures improved the amount of solubilized COD, which confirmed previously reported results. Nevertheless, solubilization mostly took place during the first 24 h. The rate of methane production in post-hydrolysis BMPs increased after 48 h hydrolysis time, but not after 24 h. The first order kinetic constant rose by 40% on average. No correlation was observed between soluble COD and downstream methane production rate, indicating a possible modification of the physical structure of the particulate solids during the hydrolytic stage.

Improving biological relevancy of transcriptional biomarkers experiments by applying the MIQE guidelines to pre-clinical and clinical trials.

The "Minimum Information for the Publication of qPCR Experiments" (MIQE [3]) guidelines are very much targeted at basic research experiments and have to our knowledge not been applied to qPCR assays carried out in the context of clinical trials. This report details the use of the MIQE qPCR app for iPhone (App Store, Apple) to assess the MIQE compliance of one clinical and five pre-clinical trials. This resulted in the need to include 14 modifications that make the guidelines more relevant for the assessment of this special type of application. We also discuss the need for flexibility, since while some parameters increase experimental quality, they also require more reagents and more time, which is not always feasible in a clinical setting.

Do we need authorized orphan drugs when compounded medications are available?

WHAT IS KNOWN AND OBJECTIVE: Orphan drugs are used to diagnose, prevent or treat a rare disease. This Commentary aims to present a number of case studies questioning the need for designating compounded medications with a long history of effective use, which is well-supported by published clinical evidence. COMMENT: Prior to the market introduction of orphan drugs, medication compounding was done in our hospital pharmacy for several rare diseases. Examples include amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (Firdapse(®)), ibuprofen for the treatment of neonatal patent ductus arteriosus (Pedea(®)) and zinc acetate for the treatment of Wilson's disease (Wilzin(®)). Several 'non-orphan' pharmaceutical products, used off-label for the treatment of rare diseases, that became orphan medicinal products include Hydrea(®) for the treatment of sickle-cell syndrome (Siklos(®)) and Viagra(®) for the treatment of pulmonary arterial hypertension (Revatio(®)). WHAT IS NEW AND CONCLUSION: In our opinion, as indicated by our examples, a better balance should be struck between the development of orphan drugs along the recently established regulatory pathways and the pragmatic use of pharmacy-compounded products and evidence-based off-label use of already available commercial products. Societal needs would be best met by focusing orphan drug development on rare diseases for which there is a high unmet medical need.

How much is the life of a cancer patient worth? A pharmaco-economic perspective.

WHAT IS KNOWN AND OBJECTIVE: Countries struggle to accommodate the introduction of new effective cancer medicines, while containing costs. Our objective is to comment on several pharmaco-economic challenges involved in determining the value of cancer medicines by reviewing cost-effectiveness thresholds for cancer medicines in several countries and by discussing the cost-effectiveness of anti-cancer biotechnology and orphan medicines. COMMENT: A literature search was carried out of PubMed, Centre for Reviews and Dissemination databases, Cochrane Database of Systematic Reviews and EconLit up to August 2009. Health technology assessment agencies in England and Scotland are willing to incur a higher cost per quality-adjusted life year for cancer medicines than for other medicines. Risk-sharing arrangements have been implemented to optimize the value of cancer medicines. The cost-effectiveness of biotechnology medicines in cancer care is challenged by their high price, and depends on the ability to identify the most responsive target population, through use of suitable biomarkers. The evaluation of orphan medicines in cancer care needs to balance the absence of an alternative therapy for a life-threatening disease against the high cost-effectiveness ratio, and usually weak clinical data. WHAT IS NEW AND CONCLUSION: Current strategies used to inform decisions on the funding of expensive anti-cancer medicines are commented on to highlight important issues and problems. Pharmaco-economic evaluation is an important tool for assessing the value of cancer medicines and to inform evidence-based decision making in cancer care. Value-judgments such as preferential consideration of anti-cancer medicines can then be made explicitly.

A computer system for contact dermatitis: graphical representation of data.

An overview is given of the computer applications we have developed over the last twelve years in the field of contact dermatitis. The dissemination of exposure lists to sensitised individuals and the development of a knowledge-based system are mentioned only briefly. Priority here is given to the explanation of the graphical representation of the patient data collected since 1978 on 12,000 patients referred to three contact dermatitis units. More than a hundred parameters of each patient have been collected in a database. Several graphs are given of these data and are discussed in detail.

UV sunlight and patch test reactions in humans.

No seasonal influence of UV sunlight on patch test reactions in humans over a period of 9 years of clinical practice was found in this retrospective study of almost 8000 patients. Although the mean UV monthly dose varies seasonally, up in the summer and down in the winter, no significant differences could be identified for patch test reactions, either for the mean number of positive test reactions or for the intensity of the skin reaction or for the id-like spread reactions seen in summer or winter. Furthermore, no short-term influences of UV exposure during the weekend preceding patch testing could be demonstrated. Therefore, reliable patch-test results can be expected at any season of the year from a general population, at least in Belgian-type climates.

Contact allergy to petrolatums. (III). Allergenicity prediction and pharmacopoeial requirements.

Several pharmacopoeias set limits on the polycyclic aromatic hydrocarbon content in petrolatum. UV absorbance measurement of aromatic extracts of petrolatum samples has been shown to be a more reliable method than direct UV absorbance measurement as prescribed by several pharmacopoeias for the determination of that content, but the presence of allergenic polycyclic aromatic hydrocarbons does not always correlate with lower UV absorbance. Biological tests are ultimately the only certain method of detecting biologically active compounds. Polycyclic aromatic hydrocarbons can also be irritant and carcinogenic. Therefore, universally uniform and very stringent limits should be set restricting their presence in pharmaceutical grade petrolatum.

Primary Hodgkin's disease of the stomach in a 72-year-old man.

Primary Hodgkin's disease of the stomach is rare, but it may occur at any age. In surgically treated patients, the prognosis is better than for adenocarcinoma. Therefore, a precise diagnosis of the gastic tumor is paramount. Endoscopic biopsy is a valuable aid. A case report is presented of a 72-year-old man in whom a diagnosis of gastric lymphoma was made preoperatively. Results were good one year after surgical therapy.