ausdoc .

com . au

6

X OCTO- MONTH library at www . ausdoc . com . au / therapy-update

2022

BER

Carmel Sparke SURGEONS have transplanted a pig ’ s heart into a man with end-stage congestive heart failure who is now “ recovering well and communicating with his loved ones ”.

The surgery on Lawrence Faucette was performed on 20 September by a team from the University of Maryland Medical Center in the US .

Several transplant hospitals had ruled him ineligible for a human heart due to peripheral vascular disease and complications with internal bleeding . So far , the pig heart was functioning well in Mr Faucette , who was breathing on his own and showing no signs of a hyperacute immune rejection , the doctors reported last month . The Maryland team said it had learned lessons from its first patient who died of multiple complications two months after xenotransplantation in early 2022 .

Tests found that porcine CMV , which causes inflammation and cell damage , had infected the organ , although there was no evidence it had spread further into the patient ’ s body .

The director of the cardiac xenotransplantation program at the university said the latest pig had been repeatedly tested for the virus , along with other antibodies , using an assay

Surgeons prepare the pig heart for transplantation .

that had not been available at the time of the first procedure .

“ It ’ s just an amazing feeling to see this pig heart work in a human [ but ] we don ’ t want to predict anything ,”

Professor Muhammad Mohiuddin said . He said the pig ’ s genome was also subjected to gene edits . This included deleting three genes responsible for a rapid

UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE

antibody-mediated rejection of pig organs by humans .

And six human genes responsible for immune acceptance of the pig heart were inserted into the genome .

One additional gene in the pig was “ knocked out ” to prevent excessive growth of the pig heart tissue .

Mr Faucette , a retired lab technician , underwent a psychiatric evaluation and met with a medical ethicist and social workers before the operation .

He said before the operation he would be taking it one day at a time .

‘ It ’ s an amazing feeling to see this work in a human .’

“ Nobody knows from this point forward . At least now I have hope and I have a chance .

“ I will fight tooth and nail for every breath I can take .”

While he was administered traditional immunosuppressive drugs , Mr Faucette also received an experimental antibody therapy called tegoprubart which attempts to block CD154 , a key protein in determining the success or failure of transplantations .

Tegoprubart is administered IV every three weeks .

More than 3000 people in the US are on the waiting list for a heart transplant .

Sarah Simpkins and Kemal Atlay THE TGA is once again urging doctors against initiating patients on semaglutide , less than three months after relaxing its prescribing advice , as limited supply struggles to keep up with surging demand .

Two weeks ago , the regulator said supply constraints for all strengths of semaglutide ( Ozempic ) would persist for the rest of the year and throughout 2024 .

It followed advice from the manufacturer Novo Nordisk that demand “ had accelerated in recent months ”, particularly for the lowdose ( 0.25mg / 0.5mg ) version , with a rapid increase in off-label use .

As a result , the TGA said prescribers should not start new patients on the drug “ unless there are no suitable alternatives or there is a compelling clinical reason to do so ” — a reversal from its advice in June .

“ For patients who are already prescribed Ozempic , consider if they can be changed to an alternative ( by consulting appropriate prescribing guidelines ) as continuous supply cannot be guaranteed ,” it said .

“ Supplies should be conserved for patients who are stabilised on Ozempic who have no other treatment options .

“ It is not known when the medicine will be available in sufficient quantities to meet the ongoing high demand .”

Dr Gary Deed , chair of the RACGP Specific Interests Diabetes group , said the ongoing supply issues were interfering with GPs ’ ability to provide optimal care .

“ The class of drugs from which it emerges will often have quite unique properties in the management of people with type 2 diabetes

— for instance , where other suitable alternatives are not exactly equivalent ,” he said .

The Brisbane GP added that dulaglutide ( Trulicity ), an alternative once-weekly GLP-1 receptor agonist , had also been affected by supply issues , while tirzepatide ( Mounjaro )

was yet to hit the private market . Switching patients to an SGLT-2 inhibitor instead was not always the best option either , he said .

“ There are unique benefits of that class , but they are sometimes not useful for the same phenotype of patients .”

‘ It took half an hour for me to explain the alternatives .’

— Dr Gary Deed

Dr Deed also said revising patients ’ diabetes management plans could be time-consuming for GPs .

“ It is frustrating for patients , especially if you have been adhering to therapy and successfully managing your complex medical problems . “ I had a conversation with a patient yesterday , and it took half an hour for me to explain the alternatives , how to access those , why they were not equivalent , why there was a cost difference .”

He stressed , however , that increasing off-label use did not mean doctors were prescribing the drug inappropriately .

Novo Nordisk revealed in August that it had made 41.7 billion Danish kroner ($ 9.3 billion ) in revenue from Ozempic sales in the first six months of 2023 . bit . ly / 3EYF8D2

FROM PAGE 1

breeds more frustration .

Fragmented care

Dr Tait says a patient who received

depot injection – based therapy for years was admitted to hospital after a psychiatrist stopped the treatments

despite the patient ’ s primary care team raising concerns about the call .

“ Another story is the mental health team will say it has gone out to visit the patient , but the patient tells the team they are okay , so it does not do anything ,” he says .

“ Or the team went and knocked on the door and nobody answered , so it assumed the person did not want to talk .

“ These are people with severe mental illness , with paranoia , with anxiety .

“ They may well not want to talk , but the issue is , do they have the capacity to refuse ?”

There are disagreements over whether certain patients have the capacity to make informed decisions about their care .

“ These interactions are tense ,” Dr Tait says .

“ We do not want to rob people of their autonomy , but if they do not have capacity and we are not treating the mental illness , that is not helping their autonomy either .”

To find a fix , the Canberra Deep End group has held workshops with primary and secondary care teams to discuss reform .

Proposals are still being finalised , but the consensus is that it is not just patients who find the mental health

care system inaccessible ; GPs have similar feelings .

“ It is a moral dilemma : we want to do the best for our patients , and we think that the secondary care services should also be working for the best of our patients ,” Dr Tait says .

“ Now , that is not to say they are not trying .

“ But there are problems in the system where clearly the system is not delivering .”