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Hormone therapy had been regarded as highly effective for the relief of hot flushes and night sweats, to treat osteoporosis and vaginal atrophy. There are several possible non-hormonal treatments, though few general practitioners recommend them and there is doubt about their efficacy. For example, clonidine, an adrenoceptor agonist originally developed for hypersensitivity, is thought to widen the thermoneutral zone and thus help to reduce hot flushes (Freedman, 2005b). Selective serotonin re-uptake inhibitors have been found to reduce hot flushes in short-term studies but the evidence is mixed, and may not be effective in healthy women (Stearns et al. Gabapentin is used to treat epilepsy, neuropathic pain and migraine, and some studies suggest it can reduce the frequency and severity of hot flushes (Toulis, Tzellos, Kouvelas, & Goulis, 2009). However, there are side effects such as dizziness and oedema and there is limited evidence to show it is effective. Tibolone is a synthetic steroid compound with mixed estrogenic, progestogenic and androgenic actions and can be used in postmenopausal women who wish to maintain amenorrhoea. It conserves bone mass and reduces the risk of vertebral and non-vertebral (but not hip) fractures particularly in patients who have already had a vertebral fracture (Rees, 2011). Cognitive Behavioural Therapy developed from the idea that automatic negative thoughts and dysfunctional beliefs can be identified and challenged (Beck, 1976) and a Cochrane review found it to be an effective treatment for general anxiety 28 (Hunot, Churchill, Teixeira, & Silva de Lima, 1996). These results suggest two conclusions: first, there is a strong psychosocial component to menopause symptoms and second, a brief intervention of this nature can help women reassign negative thoughts about menopause and teach them strategies to manage symptoms. However, it is not currently recommended or available through the National Health Service as a suitable treatment for women at menopause. That leaves Hormone Replacement Therapy, which has been the subject of controversy since the beginning of 2002. Not surprisingly, there was a rapid increase in usage, which peaked in the late 1990s (Figure 3. However, the publication of these two large epidemiological studies captured the attention of the press and the public. In addition, it was suggested that the risk of venous thromboembolism increases two-fold, with the highest risk being in the first year of use (Canonico et al. Moreover, among the women who reported adverse reactions, the most common source of information was not their clinicians but the media. Women have long believed that they have received contradictory and confusing information about menopause (Bond & Bywaters, 1998; Buchanan, Villagran, & Ragan, 2002).

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Patients must often self-fund then, the project was in an early phase, already been conceived of, applied and their healthcare from limited incomes, and few details were publicly availa shown to meet at least some of the fol and many rely heavily on privately ble. How can companies improve price the 2018 Index identifed three best setting for countries in scope No innovative practices were increase access to medicine for popu products are registered identifed. Only company to publish full details of AstraZeneca 90 this information can be used to deter the registration status of its products. It is using diferen registered ofer a key method of eval tial pricing via a customised approach uating the scope of potential access to called Mosaic Segmentation. Information can help others to determine whether products What makes this a best practice It of profles for diferent segments of can also give generic medicine manu the population. To enable this parallel fling strat of the majority of its products in scope facilitate faster registration. Yet, without a product being reg stakeholders to see which products are istered for sale in a country, it cannot What makes this a best practice It shows be made available to the people who Takeda is the only company to make an whether products have been fled for live there. This can adversely afect the explicit commitment via the Index to registration or approved for market use health of people who need new prod partake in the parallel registration of by local health authorities or regulatory ucts the most. It com help populations in countries in scope mits to prioritising and expediting the to beneft from faster access. Accessed October 27, 2018 health 2015-40: development assistance Accessed November 13, 2018. Report on the Fair vate, and out-of-pocket health spend 3 Exploring the Expansion Of the Pricing Forum 2017. The Index validates data submitted by compa information has improved signif nies against information that is publicly available about: patent cantly since 2016, with 17 compa nies placing such information in the fling/enforcement policies; patent status in low and mid public domain. Company ranking: Patents & Licensing The companies divide into fve clusters: three clear leaders, followed by three clusters in the 1 ^ 2 GlaxoSmithKline plc 3.

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In an email to a potential investor outlining the prospective acquisitions of Daraprim and another drug, Mr. Urrutia emphasized that Turing believed that the drugs could each generate 30 times their prior revenue and $2 billion or more in value for the company. At the time, these two small market 180 drugs were generating annual revenues of $6 million and $10 million. Turing also believed that Fukuzyu was under an exclusive supply agreement with 183 Impax at that time. Turing emphasized to potential investors that it expected Daraprim to remain a sole 185 source drug for at least a year, and possibly much longer. Smith to analyze the probability that a decades-old drug would face generic competition given 186 the number of units sold and net revenues received annually. Furthermore, there was only a five percent probability that a generic competitor would enter a market where fewer than 20, 000 units of a 188 drug were sold each year. Smith were not alone in their view that a small patient population was critical for remaining unchallenged after raising the price of Daraprim.

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Brown attempted repair of rectocele with a horseshoe-shaped incision in the posterior wall of the vagina. Tait, in 1887, used a mucosal flap-splitting operation for rectocele, which was later used for the anterior vaginal wall as well. However, surgery for rectocele was often confused with perineal repair (Emge and Durfee 1966). In 1888 Donald of Manchester introduced combined anterior and posterior vaginal wall repairs, perineorrhaphy and amputation of the cervix, which became the first widely used operation for genital prolapse (Loret de Mola and Carpenter 1996). He preferred (Donald 1902) plastic operations to hysterectomy and warned of the risk of vaginal vault prolapse after hysterectomy. The first attempts to fixate the vagina emphasized fixing the uterus in a position of anteversion, because retroversion was regarded as the first stage of the prolapse. Mayo (1915) described his classical technique of vaginal hysterectomy for uterine prolapse and later Heaney (1934) reported on 565 vaginal hysterectomies by a technique, which has persisted to the present. In addition to hysterectomy, both authors advocated concomitant pelvic floor repair. Zweifel is acknowledged to be the first to surgically correct vaginal prolapse by a sacrotuberal technique in 1892 (Morley and DeLancey 1988). Miller (1927) reported a transvaginal method of fixating the vagina and sacrouterine ligaments to the anterior sacrum. Subsequently Amreich (1951) described extraperitoneal posterior gluteal and later, in the 1950s, vaginal route for fixating the vagina to the sacrotuberous ligament, which is a precursor of sacrospinous ligament fixation. For correction of vaginal prolapse Ward (1938) recommended ox fascia to strengthen the round ligaments. Shaw (1948) introduced a technique with fascial support for posthysterectomy vaginal vault prolapse. Williams and Richardson (1952) introduced a transabdominal technique with ventral fixation of the vagina with transplantation of external oblique aponeurosis. Arthure and Savage (1957) described their hysteropexy and later Lane (1962) introduced a similar technique with interposing bridge between the vaginal vault and sacrum. The interposition operations did not gain popularity in this country and vaginal hysterectomy was infrequently performed after the 1910s. Vaginal anterior and posterior colporrhaphies with modifications were the most often performed operations in the 1920s and the 1930s, whereas abdominal ventrofixation of the uterus was popular in the first two decades of the 1900s. Elevated mortality led to abandonment of abdominal ventrofixation despite the fact that results of combined abdominal and vaginal approach were superior (Listo 1934).