I have been prescribing calcium and vitamin D, and latterly just vitamin D, to my patients to prevent fractures. New evidence would suggest that this strategy has been a dead loss.
A study shows that taking any combination or singular element of calcium and vitamin D provides no clinically meaningful benefit over no supplementation. The study involved 69 clinical trials overing almost 154,000 participants. 87% lived in the community and 73% were not at high risk of fractures or falls.
About 30% of people aged 65 or older and over half of those living in nursing homes experience falls at least annually. 5% of these will result in a fracture. A fracture can be the end of that persons ability to live independently. This happens in 17% of adults who are admitted to hospital after a fracture after a fall.
Low body mass index and low bone density increase the risk of fractures from falls. Calcium and vitamin D supplements are a cheap and safe intervention. Sadly the study showed that these just did not work, even in a sub-group analysis of people aged 80 or over, living in a care home, who had a previous history of fractures or falls, osteoporosis, and low vitamin D levels.
In this study, the planners aimed to see if a 2% reduction in fractures, a 0.7% reduction in hip fractures and a 2% reduction in vertebral fractures could be achieved. They didn’t rely on “statistical significance”.
The authors suggest that interventions such as balance and resistance exercise, and hazard assessment, which have been shown to reduce falls and fractures, are undertaken instead of relying on supplementation.
Unfortunately a Cochrane study has revealed that new drugs for dementia that target amyloid protein in the brain, just don’t make a clinical difference to the patient.
Although amyloid beta protein accumulates in the brain in Alzheimer’s dementia, and the drugs do help to clear this up, there is no significant difference to the mental functioning of the patients. In addition the drugs increase the risk of swelling and bleeding in the brain. The findings were reported by Francesco Nonino the lead author, who is a lead author, neurologist and epidemiologist.
The review examined 17 randomised controlled trials, involving 20,342 participants aged 70-74 with mild cognitive impairment or mild dementia from Alzheimer’s disease. Seven different monoclonal antibody drugs were tested and the outcomes assessed against placebo. The drugs all have different mechanisms of action. The studies lasted 18-24+ months. Two of the drugs, donanemab and lecanemab are licenced in the UK.
Disappointingly, there was no difference in cognitive function between the groups. There were small increases in brain swelling and bleeding, but no other side effects.
As as result there could be changes in the prescription guidance of these drugs, particularly as they are very expensive. They can cost up to £32,600 for each patient in the USA per year.
The authors recommend that other pathways be looked at for the development of new drugs and that the amyloid hypothesis be put to rest.
My comment: These drugs, particularly Donezepil, have been prescribed for quite a few years. I did see one man who had a great response to the drug. He was being cared for by his wife. He would hide under the bed thinking that he was back in the war and under attack. He got the drug and his response was fantastic. He was so good that he became her carer when she got dementia. Unfortunately he was the only patient from whom there was any noticeable change when I was a GP. In the UK the drug is only £18-30 per patient per year. I would imagine that a three month trial of the drug may be reasonable and if there is no clinical response it could be stopped. Money would be better spent on social and nursing care.No doubt clinical guidelines will be changed after this important study.Already there are calls to delay the onset of Alzheimer’sand other dementias by recommending population approaches such as measures to prevent obesity, increase exercise, decrease smoking, improve sight and hearing, and encourage social meetings and lifelong learning.If you have diabetes, good control will also reduce your risk.
Insulin is often prescribed for type two diabetes patients who need extra help with blood sugar control. Up until now, this has been injected once or twice a day. Patients are often reluctant to start insulin, however, due to concerns about the injections, dose adjustment and worries about hypoglycaemia. Once weekly insulin may be an attractive proposition for some patients.
Once weekly insulin has already been developed and has been shown to be no worse than insulin glargine or degludec. Due to potential hypoglycaemia, weekly insulin could be a problem, especially for type one patients. Nonetheless once weekly icodec has been approved for use in adults with diabetes in the Europe and Canada but it has been rejected in the US.
In trials of type two patients, once weekly insulin, used as a basal insulin, was popular with the patients, and the rates of severe hypoglycaemia were not different from those using other types of basal insulin.
Titrating up the dose in type two patients takes about 8 to 12 weeks, because the doses must be titrated cautiously. It is thought that people who are prone to experiencing ketoacidosis due to missed insulin doses, may have a lot to gain with a weekly schedule. Those who are aiming for looser blood sugar control, those with co-morbidities, and those whose insulin needs to be administered by a care giver also may benefit.
Neither insulin icodec or efsitora, the weekly insulins, are yet licenced for use in the UK at the current time. NICE will be examining the evidence and trying to determine what the place of weekly insulin should be in the NHS.
The World Heath Organisation has declared that one in six bacterial infections are now resistant to anti-biotics.
The rate of resistance has been growing rapidly with an average annual rise of 5-15% depending on the drug combinations looked at.
The problem is worse in low and middle income countries and those with weaker healthcare systems.
Resistance is now at a third of all infections in some areas.
My comment: This is terrible news. In the UK people are getting amputations when limbs could previously been saved. Some sexually transmitted infections are also incurable. Meanwhile, it becomes more important to observe basic hygiene measures such as handwashing and good kitchen habits to reduce the transmission of infection, stay home if you are ill, and use alternatives like D:Mannose if you can for urinary tract infections. Also, don’t insist or manipulate your doctor into prescribing antibiotics for mild bacterial infections or viral infections.
Four in five women get hot flushes during the menopausal years. These can cause embarrassment, lack of sleep, low mood and problems concentrating. The main group of women who can’t take HRT to treat these vasomotor symptoms is women who have a personal or strong family history of breast cancer. Worldwide only 10% of women actually use HRT for flushes.
Fezolinetantis a new drug that reduces flush frequency, severity and sleep disturbance. It blocks neurokinin in the thermoregulatory centre of the brain.
The drug works within a week of starting treatment. So far it has been compared to placebo but not HRT. There were no side effects that required withdrawal from the trial.
This sounds like a very helpful medication for those women who cannot or don’t want to take HRT.
Other Women’s Health Updates
Women in the Nurses Health Study, who had a history of Endometriosis, Adenomyosis or Uterine Fibroids had worse total mortality ratings compared to women without these conditions. Premature death extended past the reproductive years and was measured to the age of 70. The causes included an increase in gynaecological cancers, cardiac disease, respiratory disease, other cancers and other causes. The reasons for this increase in total mortality is not clear.
It has long been recognised that non- steroidal anti-inflammatory drugs raise blood pressure. If you have high blood pressure you are advised to avoid them if possible, and if you are taking them for an acute condition, let your doctor know, as it will affect their evaluation. If you don’t mention it, you could end up on more anti-hypertensive medication than you really need.
It has long been thought that paracetamol had no effect on blood pressure. I was taught this at medical school and physicians have been advising paracetamol as the drug of choice for acute conditions in hypertension for decades.
Now a new study of 110 people shows that paracetamol actually increases the blood pressure by 5 mm Hg. This was published in Circulation.
This is not a huge amount, but could potentially affect a doctor’s decision on blood pressure medication, as they tend to have certain thresholds for the initiation or increase in medication.
Let your doctor know so they can consider this information if you are getting a blood pressure check and have been taking paracetamol.
Adapted from Journal of Forensic and Legal Medicine Feb 2023Insulin murder and the case of Colin Norris by Alan Wayne Jones University of Linkoping, Sweden.
Although insulin is an essential medicine and a life saving drug, it has been used in many poisonings. These can be accidental, suicidal or to deliberately cause harm. An insulin overdose causes severe low blood sugars, and if untreated can lead to coma, irreversible brain damage and death.
Normally, in non- diabetic individuals, the beta cells in the pancreas secrete the same amounts of insulin and C peptide into the portal venous system. In the liver, the insulin is broken down faster than the C peptide, so normally there is more C peptide in the general circulation than insulin. When there is more insulin in the system than C peptide, that is a very strong indicator that insulin from a non- pancreatic source has been administered.
Sophisticated biochemical measuring systems can identify insulin analogues. This provided part of the evidence that convicted Colin Norris, a nurse, of injecting insulin into five of his patients, four of whom died as a result.
Clinical symptoms of low blood sugars occur when the blood sugars drop below 2.5 (UK) or 45 (USA), although the exact threshold can vary between individuals. If this is prolonged for up to 6 hours or more then the brain damage can be irreversible and death can occur. The hormonal response to correct low blood sugars also prolongs the QT interval in the heart electrical pacing mechanism leading to an increase in cardiac arrhythmias and sudden death.
Proof of insulin poisoning requires positive identification of the causative agent in plasma or serum samples taken from the victim before the low blood sugar is corrected.
The first proven case of murder by insulin occurred in the mid 1950s and forensic evidence was obtained from analysing tissue samples from around injection marks on the victim’s buttocks.
During an investigation into suspicious deaths caused by insulin, the entire case scenario and totality of the evidence must be carefully considered. Tissue samples around any injection marks need to be kept for later analysis of insulin and C peptide levels.
In a Leeds hospital, in September 2002, a Mrs Hall was recovering from a hip joint operation and seemed to be making good progress. In the early hours she was found unresponsive. A bedside test showed that her blood sugar was only 1.5. Although intravenous dextrose was given, she never regained consciousness and later died. She did not have diabetes. Assays showed that the insulin level was far higher than the C peptide level indicating that pharmaceutical insulin had been injected. It was believed that she may have been mistakenly injected with insulin which was kept for patients in an unlocked fridge.
Nurse Colin Norris became the prime suspect. As part of the investigation a retrospective review of other unexpected deaths and incidents which could have been due to insulin administration were found. Four incidents had occurred in the previous year when Colin Norris was on duty. Three earlier deaths had been attributed to natural causes at the time and there was no toxicological evidence that any of them had been injected with insulin. Colin Norris maintained his innocence throughout the investigation.
In October 2005 Colin Norris was charged with murdering four patients and attempting to murder a fifth by the injection of insulin. The trial started at Newcastle Crown Court in October 2007. In March 2008 he was found guilty and was sentenced to life imprisonment. He was described by the judge as a “thoroughly evil and dangerous man…arrogant and manipulative….with a real dislike of elderly patients. There cannot be any suggestion that you were motivated to hasten their ends to spare them suffering”.
After the first appeal against Norris’s conviction failed in 2009, clinical evidence emerged that spontaneous attacks of hypoglycaemia in elderly and frail patients are not as rare as the jury had been led to believe. Indeed, a literature review showed that 2-10% of elderly frail patients, who can be malnourished, with co-morbidities such as sepsis, liver disease, or kidney failure are vulnerable to attacks of hypoglycaemia.
Other weaknesses in the case were:
The insulin vials on the ward were not subject to any inventory.
No insulin or needles were found near Mrs Hall.
The fingertip blood sample showing low blood sugar was not verified with a venous blood sample.
The very high insulin level was found on an NHS assay machine, not a more accurate forensic one. Rigour in following chain of custody procedures were not done. A confirmatory sample had also not been done.
The low blood sugar had been corrected before the low C peptide versus high insulin was found.
Spontaneous hypos can indeed occur in the elderly and frail.
Another hypoglycaemia related death had occurred at the hospital but it had not been mentioned as Norris had not been on duty. Thus the police were suspected of cherry picking cases to incriminate Norris.
Toxicological evidence of hypoglycaemia was only found for Mrs Hall. Death certificates for the other suspected hypoglycaemia deaths had been attributed to old age and other natural causes.
The cause of death of Mrs Hall was brain damage due to insulin induced hypoglycaemia but it was not known if the pathologist had looked for any insulin secreting tumours.
One of the senior police officers had been involved in the Dr Harold Shipman case two years previously and he may have been primed to find another serial killer in the health profession.
The Criminal Case Review Committee, which is the official authority in the UK charged with looking into miscarriages of justice, have examined the evidence and recommended that the court of appeal have a fresh look at the case.
My comment: It will be interesting to find out what happens and what their reasoning regarding this case will be. Meanwhile, look after yourself, look after your diabetes, keep up a healthy lifestyle and keep out of hospital!
Dr Lade Smith is the first black woman president of the Royal College of Psychiatrists. She is particularly concerned about the rise in psychosis in young people. Much of this is driven by cannabis consumption, particularly from smoking it.
Far from being a benign, relaxing, recreational drug with few downsides, cannabis use in the teens can mar their future. Because cannabis is now quite potent, even use once a week, can drive a five fold increase in psychosis in male users by the age of 25.
She is concerned that recent publicity of the plus sides of cannabis oil use has increased its use overall.
If there is a family history of mental illness, if younger teenage boys use it, if it is smoked, if there are other adverse childhood experiences, then it becomes progressively unsafe. Oestrogen in girls seems to protect them somewhat from the psychotic problems that are more common in boys.
My comment: As a Police Surgeon I was very familiar with the huge increase that I saw over the years in the incidence of psychosis and drug induced psychosis in young people over the years. The brain in these people actually shrinks in size. As they usually need a lot of life long supervision from their families and medical carers, and because they usually become economically inactive for their future lives, it is not good news for the individuals, their families and society in general.
A study published in the Journal of the Canadian Medical Association in Dec 2020, has found that type two diabetics who are on Metformin have about two thirds of the risk of having a hip or knee joint replacement compared to diabetics on other medications.
The study was undertaken by Dr Zhaohua Zhu from Zhujiang Hospital in Guangzhou in China. They compared the records of over twenty thousand patients in each group and compared the duration that they were on the diabetes medications and surgical outcomes.
As they found that Metformin use was associated with a significantly reduced risk of joint replacement, this suggests a potential therapeutic effect in patients who have osteoarthritis. They recommend that randomised controlled trials are undertaken to see if there is a beneficial effect in this group.
My comment: As Metformin has already been shown to reduce cancer incidence, is inexpensive, and reasonably well tolerated both by diabetics and non-diabetics, it would seem a good idea to me for such trials to be carried out.
Adapted from Medscape Nov 20 2022 by Miriam E Tucker a freelance journalist from Washington DC.
At last humans have caught up with mice!
Since my son was diagnosed with type one diabetes, some 28 years ago, it has been possible to reverse type one diabetes in mice. At last the huge effort to find a suitable agent to use in humans, and particularly children, has been approved by the FDA.
Thank you everyone who has contributed to this marvellous discovery. The Juvenile Diabetes Research Foundation was set up with this end point in mind and they have been successful in the development of the new drug which they helped fund. The thing is that now such an agent is available, we need to be able to find the people who would most benefit from taking the drug. Thus screening for early type one diabetes is going to become crucial.
The new drug is called Teplizumab-mzwv (Tzield, Provention Bio) and it is a anti-CD 3 monoclonal antibody. It was approved in Nov 17 21 and is the first human disease modifying therapy for impeding the prevention of type one diabetes. It delayed onset by around 2 years and longer in some subjects.
It is given by an intravenous infusion once daily for 14 days and costs around $200,000 dollars for the course of treatment.
It is licensed for children over the age of 8 years. The group it is targeting is those who are asymptomatic but who have raised blood sugar levels and at least two type one diabetes antibodies. Most of those screened are first degree relatives of type ones. The JDRF is offering a screening blood test for $55. But because 85-90% of people who do develop type one diabetes don’t have a first degree relative, screening will need to be developed further.
In Bavaria, Germany, screening of all schoolchildren for type one diabetes has been done, and the organisers said that a major benefit, was that education about the signs of diabetes occurred so that diagnosis occurred before Diabetic Ketoacidosis developed. This is known to cause deaths and wears out the pancreas much faster.
In another study 2 year olds and 6 year olds in the USA and western Europe were screened for islet autoantibodies and this detected almost all of those children who developed type one diabetes by mid adolescence.
Using a genetic risk score at birth has been suggested as more cost effective by Dr William Hagopian of the Pacific Northwest Research Institute in Seattle. 10% of newborns have HLA genes that can identify 80% of those who will get childhood type one diabetes.
My comment: I’m particularly pleased to see that the JDRF has been successful because if my son has offspring they have a one in three chance of developing type one diabetes in childhood. As time goes on, it is to be hoped that the interventions will become cheaper and more effective.
