The out-of-focus bias in drug surveillance

Purpose: Existing drug safety systems with phase II and III studies and post-marketing surveillance by principle do not allow for the recognition of an important class of adverse drug reactions (ADRs). ADRs that are resistant to being detected reliably may a) appear as if they are age-related chronic diseases, which also manifest themselves in a high degree without drug treatment, b) arise in "old” drugs, c) arise during long-term application, and d) arise with the administration to frail and aged populations. Conclusions: "Silent” and multi-factorial health problems evolving from long-term drug treatment must therefore be addressed with a systematic search strategy, as a third track along with the phase II and III studies and spontaneous reporting systems which still exis

Fluid intake and changes in limb volumes in male ultra-marathoners: does fluid overload lead to peripheral oedema?

An increase in body mass due to oedema has been previously described. The aim of this study was to investigate a potential association between both fluid and electrolyte intake and the formation of peripheral oedemas. Fluid and electrolyte intakes and the changes in limb volumes in 50 male 100-km ultra-marathoners were measured. Pre- and post-race serum sodium concentration ([Na+]), serum aldosterone concentration, serum copeptin concentration, serum and urine osmolality and body mass were determined. Fluid intake, renal function parameters and urinary output, as well as the changes of volume in the extremities, were measured. The changes of volume in the limbs were measured using plethysmography. Serum [Na+] increased by 1.6%; body mass decreased by 1.9kg. Serum copeptin and aldosterone concentrations were increased. The change in serum copeptin concentration and the change in serum [Na+] correlated positively; the change in serum [Na+] and body mass correlated negatively. A mean fluid intake of 0.58L/h was positively related to running speed and negatively to post-race serum [Na+]. Total fluid intake was positively related to the changes in both arm and lower leg volumes. Running speed was positively associated with the changes in arm and lower leg volumes; race time was related to the changes in serum copeptin or aldosterone concentrations. To conclude, fluid intake was related to the changes in limb volumes, where athletes with an increased fluid intake developed an increase in limb volume

Use of placebo interventions among Swiss primary care providers

Background: Placebo interventions can have meaningful effects for patients. However, little is known about the circumstances of their use in clinical practice. We aimed to investigate to what extent and in which way Swiss primary care providers use placebo interventions. Furthermore we explored their ideas about the ethical and legal issues involved. Methods: 599 questionnaires were sent to general practitioners (GPs) and paediatricians in private practice in the Canton of Zurich in Switzerland. To allow for subgroup analysis GPs in urban, suburban, and rural areas as well as paediatricians were selected in an even ratio. Results: 233 questionnaires were completed (response rate 47%). 28% of participants reported that they never used placebo interventions. More participants used impure placebos therapeutically than pure placebos (57% versus 17%, McNemar's chi2 = 78, p<0.001). There is not one clear main reason for placebo prescription. Placebo use was communicated to patients mostly as being "a drug or a therapy" (64%). The most frequently chosen ethical premise was that they "can be used as long as the physician and the patient work together in partnership" (60% for pure and 75% for impure placebos, McNemar's chi2 = 12, p<0.001). A considerable number of participants (11-38%) were indecisive about statements regarding the ethical and legal legitimacy of using placebos. Conclusions: The data obtained from Swiss primary care providers reflect a broad variety of views about placebo interventions as well as a widespread uncertainty regarding their legitimacy. Primary care providers seem to preferentially use impure as compared to pure placebos in their daily practice. An intense debate is required on appropriate standards regarding the clinical use of placebo interventions among medical professionals

A two year study of verified spider bites in Switzerland and a review of the European spider bite literature

During a two-year study, all spider bites recorded by Swiss primary care physicians were reported to the Swiss Toxicological Information Centre and all collected spiders were identified. A total of 14 verified spider bites were recorded, involving five species from four families: Zoropsis spinimana (five cases), Cheiracanthium punctorium (four cases), Tegenaria atrica (three cases) and one case of Malthonica ferruginea (= Tegenaria ferruginea) (both Agelenidae), and one case of Amaurobius ferox (Amaurobiidae). The bites of all spider species produced relatively mild symptoms. Local symptoms such as moderate to severe pain, circumscribed swelling and redness were the only effects in most cases. Systemic symptoms were rare. There was complete recovery in all cases and all lesions healed completely without further damage or secondary disorders. Following a review of the European spider bite literature, the number of spider species capable of biting humans in Europe is considered to be much larger than could be concluded from this study. Most spider bites are restricted to species living synanthropically, thus promoted by climate and habitat change. The annual frequency of spider bites in Switzerland is estimated at 10-100 bites per million inhabitants, but this is predicted to increase due to the continuous arrival of new alien species, many of which have a high potential to establish in urban areas

Placebo interventions in practice: a questionnaire survey on the attitudes of patients and physicians

GPs rather underestimate the openness of their patients to non-specific therapies. However, patients want to be appropriately informed. Developing specific professional standards could help physicians to harness the 'power of the placebo', while remaining authentic and credibl

The out-of-focus bias in drug surveillance

PURPOSE: Existing drug safety systems with phase II and III studies and post-marketing surveillance by principle do not allow for the recognition of an important class of adverse drug reactions (ADRs). ADRs that are resistant to being detected reliably may a) appear as if they are age-related chronic diseases, which also manifest themselves in a high degree without drug treatment, b) arise in "old" drugs, c) arise during long-term application, and d) arise with the administration to frail and aged populations. CONCLUSIONS: "Silent" and multi-factorial health problems evolving from long-term drug treatment must therefore be addressed with a systematic search strategy, as a third track along with the phase II and III studies and spontaneous reporting systems which still exist