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Discover Australia's Gold Coast, including beautiful beaches at Surfer's Paradise, Coolangatta and Burleigh Heads, animals at Currumbin Wildlife Sanctuary and Gold. Ask Gold Coast Theme Parks Question. Do you have a question about visiting Gold Coast theme parks? Wondering which one is best for your family? Posted by Frank Barrett, Travel Editor, The Mail on Sunday. If you fancy a theme park holiday further afield, Florida is once again proving popular with British. First, let me preface this by saying that I am not anti-Ocrevus. As I’ve stated on these pages any number of times, it is my firmly held belief that MS patient.

Wheelchair Kamikaze(What follows is my analysis of the potential promises and pitfalls associated with the new MS drug Ocrevus (Ocrelizumab). For those who have not already done so, I urge you to read – or at least scan – the interview I conducted with Dr. Peter Chin, one of the pioneering researchers who worked on this drug. Chin is the Group Medical Director of Neuroscience at the pharmaceutical company that makes ocrelizumab, Genentech – click here for the interview)Ocrevus, a new MS drug which was approved by the FDA on March 2.

MS treatment landscape. Particularly heralded is the drug’s success in clinical studies in treating Primary Progressive Multiple Sclerosis (PPMS), a pernicious subtype of MS that currently has no approved therapies. Assessing the overall potential of Ocrevus is more difficult than with most new drugs, as the therapy has a complicated history that must be considered when synthesizing informed views about it.

Ocrevus, which will be marketed under the brand name Ocrevus, is a close sibling of the much older drug Rituxan (rituximab), whose mechanism of action Ocrevus closely mirrors. Rituximab, which is manufactured by the same company that makes Ocrevus, is already being used in many parts of the world as an effective MS therapy, even though it was never officially approved for this purpose. The reasons why Ocrevus rather than rituximab was advanced in studies as an MS therapy are somewhat controversial; complicating matters further are Ocrevus’s failure in trials for use in treating other autoimmune diseases (lupus and rheumatoid arthritis). Therefore, when attempting to make a sober assessment of Ocrevus, one must look not only at the drug itself, but also at how it currently came to be on the verge of FDA approval. How To Be Really Bad watch online in english with english subtitles in 4320p.

First, let’s look at Ocrevus itself, in terms of how the drug works and what recent clinical trials reveal about its effectiveness in the treatment of both relapsing and primary progressive multiple sclerosis. Ocrevus is the first B cell therapy for MS proven to be effective in late stage clinical trials. In very simplistic terms, the human immune system is comprised chiefly of 2 types of cells, T cells and B cells, which each use different mechanisms to attack and kill invading bacteria or viruses. Until very recently, the vast majority of MS researchers, who see MS as an autoimmune disease in which the immune system turns against the body’s own cells, considered the multiple sclerosis disease process to be driven almost exclusively by T cells. MS drugs such as Tysabri and Gilenya were designed to specifically target these cells. B cells were given short shrift, and were largely dismissed as having no real relevance in the MS disease process. The success of Ocrevus – a drug which destroys B cells – in treating MS has upended these prior assumptions and has forced researchers to rethink their multiple sclerosis disease models.

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In clinical trials, Ocrevus, an intravenous drug administered approximately every 6 months, proved to be remarkably effective in treating relapsing multiple sclerosis, and even had a modest effect on PPMS. Let’s look at the actual trial results. Two separate trials were conducted testing Ocrevus against the interferon drug Rebif in patients with relapsing multiple sclerosis. These two trials were called OPERA 1 and OPERA 2 (click here). Both two- year trials involved one group of patients taking Ocrevus and another taking the interferon drug Rebif, and comparisons were made as to the overall effectiveness of Ocrevus versus the interferon drug.

The results were very impressive. Compared to the Rebif treated patients, the Ocrevus trial subjects experienced a reduction in relapse rates of 4.

Additionally, there was a 4. These results rival or surpass any of the other MS drugs currently on the market. There were no significant differences in the number of adverse events (bad side effects) between the Ocrevus and Rebif treated patient populations in the relapsing multiple sclerosis trials. The Ocrevus PPMS trial was named ORATORIO (click here).

In other words, twice as many trial subjects received Ocrevus than received placebo. The highlight of this study was that the Ocrevus treated patients experienced a 2.

Specifically, 2. 9. Ocrevus treated patients and 3. This is the first time in a placebo- controlled scientific trial that any multiple sclerosis drug has displayed effectiveness in slowing down the progression of disability in Primary Progressive patients. Ocrevus also displayed efficacy over placebo in a number of other outcome measures as well, including the timed 2.

As I discussed with Dr. Chin during our interview, it’s important to understand that Ocrevus did not reverse or even stop the progression of disability in trial subjects. It slowed progression by about 2.

What does this mean for patients in a real- world setting? Well, speaking strictly in a broadly hypothetical basis, if an individual PPMS patient left untreated might need a cane four years after diagnosis, that same patient, if responsive to Ocrevus, might not need a cane for five years. Again, this is strictly a hypothetical case; PPMS effects patients in widely varying degrees of severity. Additionally, the ORATORIO trial only lasted 2 and half years. How the drug's effectiveness manifests over longer periods of time is not yet understood.

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Unlike the relapsing multiple sclerosis Ocrevus trials, the PPMS trial did reveal some potentially troubling adverse events. Opportunistic infections (mostly respiratory infections and oral herpes) were more common in Ocrevus than placebo, and the rate of cancer in Ocrevus treated patients was approximately 3 times that found in placebo treated patients, 2. Though Genentech says that no direct causal relationship between the cancers in Ocrevus treated patients could be established, the fact that slightly more than 1 in 5. There are also some concerns regarding the design ORATORIO study. Back in the mid- 2.

Genentech conducted a PPMS trial using rituximab, which at first was deemed a failure. Later review of the trial data revealed, though, that a subset of PPMS patients did appear to gain benefit from rituximab therapy (click here). These patients were generally younger than 5. MRIs. It’s generally thought that patients fitting this description account for between 1. PPMS population. The Ocrevus PPMS trial, though, included about 2. PPMSer’s. This means that the ORATORIO trial was heavily weighted with patients who were likely to respond to Ocrevus, since the drug acts in much the same way as rituximab.

The Ocrevus PPMS trial was not designed to discern differences in the effectiveness of the drug between patients with enhancing lesions and those without, but Genentech says there was a “directional consistency” to the trial results, suggesting that the drug was effective in all patient subgroups to one degree or another. Still, the fact that the trial was frontloaded with likely responders is another eyebrow raiser, and may be something that the FDA looks at when making its approval decisions.

Okay, now that we’ve looked at the Ocrevus MS trials themselves, let’s dive into the history of the drug. Back in the early 2. MS researchers began investigating whether therapies that destroy B cells might be effective in treating MS. As mentioned earlier, at the time this with a rather radical idea. The drug that was chosen for study was Rituxan (whose generic name is rituximab – click here), a drug developed by Genentech years earlier that had been approved in 1. Hodgkin’s lymphoma and certain types of leukemia. Rituximab, like Ocrevus, works by zeroing in on a protein found on most types of B cells, called CD2.

Though both drugs target and kill B cells, they do so in slightly different ways, and these differences may result in variances in safety and efficacy. Think of the drugs as two hitmen; one likes to slit his victims throats, the other prefers to strangle them. Both get the job done, but their differing killing techniques might effect witnesses differently. In the case of Ocrevus and rituximab, these differences may effect the actions of other immune cells, thus accounting for possible differences in the safety and efficacy of the drugs. In the mid- 2. 00.

MS researchers put rituximab to the test by using it in “proof of concept” trials in patients with RRMS and PPMS. When the trial results were revealed in 2. MS, but not effective in treating PPMS (click here and here). It’s important to note that the RRMS trials were small, early stage trials, but the PPMS trial was larger and later stage. As mentioned earlier, later parsing of the PPMS data did reveal a subgroup of patients on whom the drug appeared to have some positive effect. Given the success of the rituximab RRMS trials, the fact that a subset of the PPMS trial population appeared to benefit from the drug, and rituximab’s long history as a successful oncology drug, it’s reasonable to assume that the drug would have been greenlighted for further development as an MS treatment.

Instead, all development of rituximab as an MS treatment was halted, and the focus shifted instead to Ocrevus, a new experimental Genentech product that also targeted B cells via the CD2. While there is some perfectly valid scientific rationale for this choice, many facts and circumstances point to financial motivations playing an oversized role in the decision to advance Ocrevus rather than rituximab as a potential treatment for MS. The scientific rationale for choosing to proceed with Ocrevus is that the drug is comprised primarily of human proteins (the drug is a “humanized” monoclonal antibody), while rituximab contains a mix of mouse and human proteins (making it a “chimeric” monoclonal antibody, meaning that it contains proteins from more than one species). Theoretically, a humanized molecule should be better tolerated by patients than a chimeric drug, especially when used for treating chronic diseases which require continued administrations of the drug.

Munster v All Blacks 1. During that time, they resisted the best that Ireland, Ulster and Leinster (admittedly with fewer opportunities) could throw at them so this country was still waiting for any team to put one over on the All Blacks when Graham Mourie’s men arrived in Limerick on October 3.

There is always hope but in truth Munster supporters had little else to encourage them as the fateful day dawned. Whereas the New Zealanders had disposed of Cambridge University, Cardiff, West Wales and London Counties with comparative ease, Munster’s preparations had been confined to a couple of games in London where their level of performance, to put it mildly, was a long way short of what would be required to enjoy even a degree of respectability against the All Blacks. They were hammered by Middlesex County and scraped a draw with London Irish. Ever before those two games, things hadn’t been going according to plan. Tom Kiernan had coached Munster for three seasons in the mid- 7. Branch President, a role he duly completed at the end of the 1. EA OF EMOTION: Munster’s players and supporters celebrate a famous victory.

However, when coach Des Barry resigned for personal reasons, Munster turned once again to Kiernan. Being the great Munster man that he was and remains, Tom was happy to oblige although as an extremely shrewd observer of the game, one also suspected that he spotted something special in this group of players that had escaped most peoples’ attention. He refused to be dismayed by what he saw in the games in London, instead regarding them as crucial in the build- up to the All Blacks encounter. He was, in fact, ahead of his time, as he laid his hands on video footage of the All Blacks games, something unheard of back in those days, nor was he averse to the idea of making changes in key positions. A major case in point was the introduction of London Irish loose- head prop Les White of whom little was known in Munster rugby circles but who convinced the coaching team he was the ideal man to fill a troublesome position. Kiernan was also being confronted by many other difficult issues. The team he envisaged taking the field against the tourists was composed of six players (Larry Moloney, Seamus Dennison, Gerry Mc.

Loughlin, Pat Whelan, Brendan Foley and Colm Tucker) based in Limerick, four (Greg Barrett, Jimmy Bowen, Moss Finn and Christy Cantillon) in Cork, four more (Donal Canniffe, Tony Ward, Moss Keane and Donal Spring) in Dublin and Les White who, according to Keane, “hailed from somewhere in England, at that time nobody knew where”. Always bearing in mind that the game then was totally amateur and these guys worked for a living, for most people it would have been impossible to bring them all together on a regular basis for six weeks before the match. But the level of respect for Kiernan was so immense that the group would have walked on the proverbial bed of nails for him if he so requested. So they turned up every Wednesday in Fermoy — a kind of halfway house for the guys travelling from three different locations and over appreciable distances. Those sessions helped to forge a wonderful team spirit. After all, guys who had been slogging away at work only a short few hours previously would hardly make that kind of sacrifice unless they meant business. October 3. 1, 1. 97.

Munster who could indulge in their traditional approach sometimes described rather vulgarly as “boot, bite and bollock” and, who knows, with the fanatical Thomond Park crowd cheering them on, anything could happen. Ironically, though, the wind and rain had given way to a clear, blue sky and altogether perfect conditions in good time for the kick- off. Surely, now, that was Munster’s last hope gone — but that didn’t deter more than 1. Thomond Park and somehow finding a spot to view the action. The vantage points included hundreds seated on the 2. Ballynanty end that have since been demolished.

The atmosphere was absolutely electric as the teams took the field, the All Blacks performed the Haka and the Welsh referee Corris Thomas got things under way. The first few skirmishes saw the teams sizing each other up before an incident that was to be recorded in song and story occurred, described here — with just the slightest touch of hyperbole!

He came from the Garryowen club which might explain his subsequent actions — to join that club, so it has been said, one must walk barefooted over broken glass, charge naked through searing fires, run the severest gauntlets and, as a final test of manhood, prepare with unfaltering gaze to make a catch of the highest ball ever kicked while aware that at least eight thundering members of your own team are about to knock you down, trample all over you and into the bargain hiss nasty words at you because you forgot to cry out . That was the moment we knew we could win the game.” Kiernan also acknowledged the importance of “The Tackle”.

He said: “Tackling is as integral a part of rugby as is a majestic centre three- quarter break. There were two noteworthy tackles during the match by Seamus Dennison.

He was injured in the first and I thought he might have to come off. But he repeated the tackle some minutes later.”Many years on, Stuart Wilson vividly recalled the Dennison tackles and spoke about them in remarkable detail and with commendable honesty: “The move involved me coming in from the blind side wing and it had been working very well on tour. It was a workable move and it was paying off so we just kept rolling it out.

Against Munster, the gap opened up brilliantly as it was supposed to except that there was this little guy called Seamus Dennison sitting there in front of me.“He just basically smacked the living daylights out of me. I dusted myself off and thought, I don’t want to have to do that again. Ten minutes later, we called the same move again thinking we’d change it slightly but, no, it didn’t work and I got hammered again.”The game was 1. Munster rugby was scored.

Tom Kiernan recalled: “It came from a great piece of anticipation by Bowen who in the first place had to run around his man to get to Ward’s kick ahead. He then beat two men and when finally tackled, managed to keep his balance and deliver the ball to Cantillon who went on to score. All of this was evidence of sharpness on Bowen’s part.”Very soon it would be 9- 0.

In the first five minutes, a towering garryowen by skipper Canniffe had exposed the vulnerability of the New Zealand rearguard under the high ball. They were to be examined once or twice more but it was from a long range but badly struck penalty attempt by Ward that full- back Brian Mc. Kechnie knocked on some 1. Cantillon had touched down a few minutes earlier. You could sense White, Whelan, Mc. Loughlin and co in the front five of the Munster scrum smacking their lips as they settled for the scrum. A quick, straight put- in by Canniffe, a well controlled heel, a smart pass by the scrum- half to Ward and the inevitability of a drop goal.

And that’s exactly what happened. The All Blacks enjoyed the majority of forward possession but the harder they tried, the more they fell into the trap set by the wily Kiernan and so brilliantly carried out by every member of the Munster team. Watch The Allins in english with english subtitles 1280.

The tourists might have edged the line- out contest through Andy Haden and Frank Oliver but scrum- half Mark Donaldson endured a miserable afternoon as the Munster forwards poured through and buried him in the Thomond Park turf. As the minutes passed and the All Blacks became more and more unsure as to what to try next, the Thomond Park hordes chanted “Munster- Munster–Munster” to an ever increasing crescendo until with 1. And then .. Eventually, he stumbled over the ball as it crossed the line and nervously conceded a five- metre scrum. The Munster heel was disrupted but the ruck was won, Tucker gained possession and slipped a lovely little pass to Ward whose gifted feet and speed of thought enabled him in a twinkle to drop a goal although surrounded by a swarm of black jerseys. So the game entered its final 1. All Blacks needing three scores to win and, of course, that was never going to happen.

Munster knew this, so, too, did the All Blacks. Stu Wilson admitted as much as he explained his part in Wardy’s second drop goal: “Tony Ward banged it down, it bounced a little bit, jigged here, jigged there, and I stumbled, fell over, and all of a sudden the heat was on me. They were good chasers. A kick is a kick — but if you have lots of good chasers on it, they make bad kicks look good.

I looked up and realised — I’m not going to run out of here so I just dotted it down. I wasn’t going to run that ball back out at them because five of those mad guys were coming down the track at me and I’m thinking, I’m being hit by these guys all day and I’m looking after my body, thank you.

Of course it was a five- yard scrum and Ward banged over another drop goal. That was it, there was the game”. The final whistle duly sounded with Munster 1.

Bodies were embraced, faces were kissed, backs were pummelled, you name it, the gauntlet had to be walked. Even the All Blacks seemed impressed with the sense of joy being released all about them. Andy Haden recalled “the sea of red supporters all over the pitch after the game, you could hardly get off for the wave of celebration that was going on. The whole of Thomond Park glowed in the warmth that someone had put one over on the Blacks.”Controversially, the All Blacks coach, Jack Gleeson (usually a man capable of accepting the good with the bad and who passed away of cancer within 1.

We were up against a team of kamikaze tacklers,” he lamented. Kamikaze pilots were very brave men.

That’s what I took out of that. I didn’t think it was a criticism of Munster.”And Stuart Wilson? We had been travelling through the UK and winning all our games.

We were playing a nice, open style. But we had never met a team that could get up in our faces and tackle us off the field. Every time you got the ball, you didn’t get one player tackling you, you got four.