EUSA, through a vehicle called Huxley Pharmaceuticals, sold the rights to 3,4-DAPP to BioMarin in 2009, the same year that 3,4-DAPP was approved in Europe under the new name Firdapse.The licensing of Firdapse in 2010 in Europe led to a sharp increase in price for the drug. In some cases, this has led to hospitals using an unlicensed form rather than the licensed agent, as the price difference proved prohibitive. BioMarin has been criticized for licensing the drug on the basis of previously conducted research, and yet charging exorbitantly for it. A group of UK neurologists and pediatricians petitioned to prime minister David Cameron in an open letter to review the situation. The company responded that it submitted the licensing request at the suggestion of the French government, and points out that the increased cost of a licensed drug also means that it is monitored by regulatory authorities (e.g. for uncommon side effects), a process that was previously not present in Europe. A 2011 Cochrane review compared the cost of the 3,4-DAP and 3,4-DAPP in the UK and found an average price for 3,4-DAP base of £1/tablet and an average price for 3,4-DAP phosphate of £20/tablet; and the authors estimated a yearly cost per person of £730 for the base versus £29,448 for the phosphate formulation.Meanwhile, in Europe, a task force of neurologists had recommended 3,4-DAP as the firstline treatment for LEMS symptoms in 2006, even though there was no approved form for marketing; it was being supplied ad hoc.
A perforated eardrum (tympanic membrane perforation) is a hole in the eardrum. It can be caused by infection (otitis media), trauma, overpressure (loud noise), inappropriate ear clearing, and changes in middle ear pressure. An otoscope can be used to view the eardrum to diagnose a perforation. Perforations may heal naturally, or require surgery. Presentation
A perforated eardrum leads to conductive hearing loss, which is usually temporary. Other symptoms may include tinnitus, ear pain, vertigo, or a discharge of mucus. Nausea and/or vomiting secondary to vertigo may occur. Causes
A perforated eardrum can have one of many causes, such as:

infection (otitis media). This infection may then spread through the middle ear, and may reoccur. trauma. This may be caused by trying to clean ear wax with sharp instruments. It may also occur due to surgical complications. overpressure (loud noise or shockwave from an explosion). inappropriate ear clearing. flying with a severe cold, due to changes in air pressure and blocked Eustachian tubes resulting from the cold. This is especially true on landing. Diagnosis
An otoscope can be used to look at the ear canal. This gives a view of the ear canal and eardrum, so that a perforated eardrum can be seen. Tympanometry may also be used. Treatment
Conservative management
A perforated eardrum often heals naturally. It may heal in a few weeks, or may take up to a few months. Surgery
Some perforations require surgical intervention. This may take the form of a paper patch to promote healing (a simple procedure by an ear, nose and throat specialist), or surgery (tympanoplasty).