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Eli Lilly’s Cialis (

tadalafil

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Cialis slowed the progression of heart failure in sheep models of the disease and reversed breathlessness, one of the most troublesome symptoms, the researchers reported in the journal Scientific Reports.

This class of drugs, PDE5 inhibitors, which also includes Pfizer’s Viagra and Bayer’s Levitra, was originally developed for cardiac disease.

Then the scientists developing Viagra discovered the drug relieved ED.

“We do have limited evidence from human trials and epidemiological studies that show Tadalafil can be effective in treating heart failure,” said the study’s lead author, Andrew Trafford, in a statement. “This study provides further confirmation, adds mechanistic details and demonstrates that Tadalafil could now be a possible therapy for heart failure.” It’s possible that patients taking Cialis for ED have already unknowingly benefited from the drug’s protective effect on the heart, he added. Heart failure is characterized by the heart’s inability to pump enough blood to meet the body’s needs, which can lead to fluid accumulation in the lungs and cause the feeling of being short of breath. Trafford’s team used sheep to study the effects of PDE5 inhibition because their hearts are similar to human hearts.

After inducing heart failure in the animals, the team administered Cialis at a dose similar to what’s used to treat ED in people.

They observed that Cialis restored the heart’s ability to respond to adrenaline—and that improved its ability to pump blood. Most heart failure medications can slow the progression of the disease and lower the probability of deadly cardiac events.

But actually reversing heart failure is difficult, especially without surgery or the assistance of medical devices.

Various groups of scientists are exploring methods for reversing heart failure with drugs. A team at Imperial College London recently found that blocking the MAP4K4 protein could reduce heart damage. In a 2017 Nature study, Baylor College of Medicine researchers discovered that the Hippo signaling pathway can prevent damaged heart muscle from repairing itself, and by blocking it, they restored pumping ability in mouse hearts.

But the University of Manchester researchers believe the best strategy may be to return to the original goal in PDE5 inhibition.

“We seem to have gone full-circle, with findings from recent studies suggesting that [ED drugs] may be effective in the treatment of some cialis for sale ebay forms of heart disease—in this case, heart failure,” said Metin Avkiran, associate medical director of the British Heart Foundation, which funded the study. "The evidence from this study, that a Viagra-like drug could reverse heart failure, should encourage further research in humans to determine if such drugs may help to save and improve lives.” Erections after prostatectomy surgery: does Viagra still work?

In this blog for a non-medical audience, Alastair Lamb, Senior Fellow in Robotic surgery and Consultant Urologist at Oxford University Hospitals, and Altan Omer, Pelvic GU-Oncology fellow, look at the evidence for use of PDE5 inhibitors (Viagra, Cialis & Levitra) for penile rehabilitation after prostate cancer surgery. Some 6,500 radical prostatectomies are performed every year in the UK (British Association A relationship between two characteristics, such that as one changes, the other changes in a predictable way. For example, statistics demonstrate that there is an association between smoking and lung cancer.

In a positive association, one quantity increases as the other one increases (as with smoking and lung cancer).

In a negative association, an increase in one quantity corresponds to a decrease in the other.

Association does not necessarily mean that one thing causes the other. While approximately half of these men have pre-existing erectile dysfunction, over 50% of the other half can expect to lose natural erections after prostatectomy surgery, especially if their cancers are locally advanced and require wide clearance to ensure removal of the whole tumour. There’s pretty good evidence to show that men can continue to recover erectile function up to two years after prostatectomy surgery (Montorsi et al., 2014), which we believe is partly because it takes time for the bruising and scar tissue after surgery to settle down. But if spontaneous erections do not recover by this point then it is unlikely that they will do so thereafter.

Conversely, there is good evidence that drugs such as Viagra can be used to enhance erections after surgery and that, even if such drugs do not work – for example if the nerves have been removed to maximise cancer clearance – mechanical devices such as vacuum pumps, cavaject injections into the side of the penis or MUSE therapy (small tablets inserted into the end of the urethra) are effective.

The question therefore remains as to whether longer term recovery of spontaneous erections can be assisted by such devices and particularly by the use of PDE5 inhibitors.

This is a process generally known as “penile rehabilitation”.

The concept is that men need to ‘use’ their penises in order to speed up recovery of the blood vessels and nerves that are essential for erections, indeed

that

lack of use may inhibit recovery. This Cochrane review pulled together randomised trials testing the effect of PDE5i on erectile function after radical prostatectomy (Philippou et al., 2018). There were eight randomised Randomization is the process of randomly dividing into groups the people taking part in a trial.

One group (the intervention group) will be given the intervention being tested (for example a drug, surgery, or exercise) and compared with a group which does not receive the intervention (the control group).

trials Clinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used.

No matter how promising a new treatment may appear during tests in a laboratory, it

must

go through clinical trials before its benefits and risks can really be known.

including 1699 men and the drugs used were either Viagra (sildenafil), Cialis (tadalafil) or Levitra (vardenafil). The review found no evidence to support penile rehabilitation, defined as an improvement in erectile function, off drug, at the end of the period of follow up (one to two years) compared to a control group who had not received any drug.

The authors did note however that the quality of evidence The certainty (or quality) of evidence is the extent to which we can be confident that what the research tells us about a particular treatment effect is likely to be accurate.

Concerns about factors such as bias can reduce the certainty of the evidence.

Evidence may be of high certainty; moderate certainty; low certainty or very-low certainty.

Cochrane has adopted the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation) for assessing certainty (or quality) of evidence. Find cialis for sale ebay out more here: https://training.cochrane.org/grade-approach was poor, mainly because of a lack predefined outcomes Outcomes are measures of health (for example quality of life, pain, blood sugar levels) that can be used to assess the effectiveness and safety of a treatment or other intervention (for example a drug, surgery, or exercise).

In research, the outcomes considered most important are ‘primary outcomes’ and those considered less important are ‘secondary outcomes’.

and inconsistency in reporting standards (varying definitions of potency, different follow-up durations, multiple modes of assessment including both physician and patient-reported outcomes etc).

All men in these studies had some form of

nerve-sparing

performed during their surgery so this review was not able to assess the effect of nerve-sparing on subsequent recovery of erections as there was no control group to compare to.

Previous studies have convincingly demonstrated the critical nature of nerve-sparing (Patel et al., 2011).

The decision to undertake nerve-sparing is made in advance by the surgeon and depends on the extent of cancer. Robotic surgery has allowed more precise and meticulous surgical dissection of the surrounding layers of the prostate. Indeed, 80% of UK prostatectomies are now completed with a da Vinci robot, the remainder split evenly between laparoscopic and open surgery. The outer layers of the prostate are a bit like an onion with several layers. The layer containing the nerves is like the brown skin on the onion and the surgeon can choose to cut inside this layer to leave the brown skin (or nerve layer) in place. The outer layers of the prostate are a bit like an onion with several layers. The layer containing the nerves is like the brown skin on the onion and the surgeon can choose to cut inside this layer to leave the brown skin (or nerve layer) in place.

However, when there is a lot of cancer there is a real possibility of leaving some cancer cells behind if this close cialis for sale ebay approach is taken, and so the surgeon instead chooses intentionally to take this outer layer with the prostate – the brown skin stays on the onion. So, while it may increase the risk A way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%).

This measure is good no matter the incidence of events i.e. of prostate tissue being left behind (

which

incidentally, is one of the reasons why the PSA may remain high post-operatively), sparing the nerves is a critical step for preservation of erectile function, and men who undergo an intentional non-nerve-sparing procedure should always be warned of the inevitability of erectile dysfunction after surgery.

Of course, for those men who have already have erectile dysfunction before surgery, no amount of nerve sparing will return

natural

erections. A box of four 100mg tablets (Viagra, Pfizer) will cost the NHS or you (by private prescription) ?23.50 per box.

However, since December 2017 in the US, and amazingly since June 2013 in the UK, it has been legal for other drug manufacturers to make generic sildenafil and so, with a private prescription you can now pick up a box of 4 x 100mg sildenafil citrate tables for as little as 79p, a thirty-fold price reduction. The NHS is slowly waking up to this but still official NHS guidance only permits one packet of four tables per month for those who meet strict erectile dysfunction criteria.

We hope this will change soon, given that 11 boxes could be purchased for the ?8.80 standard NHS prescription charge!

Furthermore, Cialis also came off patent in December 2018 in the US and we can therefore expect generic tadalafil , which currently costs ?54.99 for a box of 28 x 2.5mg – cialis is generally taken daily due to its longer half-life – to come down to similar prices. Increasing availability of these previously expensive drugs is a tremendous help for men who have undergone radical prostate surgery.

Despite the uncertainty regarding penile rehabilitation, there is no doubt that real-time erections often improve while on Viagra (or Cialis or Levitra etc) and so straightforward access to these drugs is essential for a speedy return to a functioning sex life after cancer, for those who want it. Join in the conversation on Twitter with @CochraneUK or leave a comment on the blog. Alastair Lamb and Altan Omer have nothing to disclose.

Omer MD FEBU is a Pelvic Uro-Oncology and Robotic Surgery Fellow at the Churchill Hospital, Oxford.

Mr Alastair D Lamb, MA(Oxon), MBChB, PhD(Cantab), FRCS(Urol) is a Cancer Research UK Clinician Scientist, Senior Fellow in Robotic Surgery and Honorary Consultant Urologist at the Nuffield Department of Surgery, University of Oxford and Oxford University Hospitals NHS Foundation Trust, UK.

My clinical focus is to deliver excellent and timely prostate cancer care to men referred to our team from the Oxford regional area, focussing on state-of-the-art diagnostics with multiparametric MRI and targeted transperineal biopsies, followed by robotic-radical prostatectomy (RARP) or indeed active surveillance where appropriate.



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