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18th May 2022
The PCSK9 inhibitor, alirocumab, given twice weekly in combination with a statin, to patients who underwent urgent percutaneous coronary intervention (PCI) after an acute myocardial infarction (MI) resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks compared to placebo. This was the conclusion of a randomised clinical trial by teams from Switzerland and Denmark.
It has been previously shown that the use of maximal dose statin therapy can produce a significant regression of coronary atherosclerosis when measured by the percent atheroma volume. Patients who have experienced an MI continue to be at risk of a subsequent event, highlighting the continued need for statin therapy. For example, one study of post-MI patients found how such individuals continue to be at risk of cardiovascular events beyond the first year after their initial MI. A further reason to continue statin therapy and to hopefully see regression of coronary atherosclerosis, comes from a study in those with acute coronary syndrome. The study revealed that subsequent major adverse cardiovascular events were equally attributable to recurrence at the site of initial or culprit lesions and to non-culprit or non-infarct-related arteries. It has also been shown that the combination of alirocumab and high dose statins in patients who experienced acute coronary syndrome 1 to 12 months earlier, reduces the risk of recurrent ischaemic cardiovascular events compared to placebo.
Although combining alirocumab with a statin reduces subsequent recurrent adverse cardiovascular events, little is known about how this combination impacts on plaque burden and composition. As a result, for the present study, the researchers undertook the Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction (PACMAN-AMI) randomised trial. The study recruited adult patients (> 18 years) who underwent urgent percutaneous coronary intervention (PCI) of the culprit lesion for treatment of ST-elevation MI. Patients were randomised 1:1 to biweekly subcutaneous alirocumab (150mg) or placebo and which was started less than 24 hours after the PCI and given in combination with rosuvastatin 20mg daily for a total of 52 weeks. The availability of various imaging modalities enabled the team to take a closer look at how the combination therapy affected plaques. They used intravascular ultrasonography (IVUS), near-infrared spectroscopy and optical coherence tomography (OCT) on two non-infarct-related coronary arteries both at baseline and at the end of the study. The IVUS was used to assess changes in percent atheroma volume (PAV), whereas near-infrared provided a measure of the maximum lipid core burden index. This latter metric, provides an assessment of the lipid content of a plaque, such that lower values are associated with a reduced risk of adverse events. OCT can be used to assess minimal fibrous cap thickness with a thicker plaque being more stable and therefore less likely to rupture.
The primary outcome for the study was the change in IVUS PAV from baseline to week 52 and two secondary outcomes were changes in maximum lipid core burden index and OCT-derived minimal fibrous cap thickness.
Alirocumab and changes in percent atheroma volume
A total of 300 patients with a mean age of 58.5 years (18.7% women) and an overall mean LDL cholesterol level of 3.94mmol/l were randomised to alirocumab or placebo.
After 52 weeks of therapy, the mean LDL cholesterol level was 1.91mmol/l in the placebo group and 0.60mmol/l in the alirocumab group (p < 0.001).
For the primary endpoint, the change in mean PAV was significantly greater for alirocumab compared to placebo (-2.13% vs -0.92%, p < 0.001). The lipid core burden was also significantly reduced with alirocumab (mean change -79.4 vs -37.60, alirocumab vs placebo, p = 0.006). Finally, fibrous cap thickness also significantly increased with alirocumab compared to placebo (p = 0.01).
Based on these findings, the authors concluded by calling for future studies to examine whether the changes observed with alirocumab would lead to an improvement of clinical outcomes for patients.
Räber L et al. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA 2022
13th May 2022
Cancer is the second leading cause of death globally and in 2018, it accounted for approximately 9.6 million deaths. Although cancer can strike at any age, many types of cancer become more prevalent with increasing age. However, recent research has found that for most adults, cancer does not have to be an inevitable consequence of growing older. In fact, adoption of healthy lifestyle measures based on a combination of exercise, diet, smoking status, alcohol consumption, and anthropometry, in other words, simple behavioural modifications, have been shown to produce a sizeable reduction in the risk of some cancers. Among healthy interventions, there is evidence that physical activity is associated with a lower risk of several cancers. Equally, use of vitamin D supplements has some evidence to support its use in reducing the incidence of advanced (metastatic or fatal) cancer. Finally, an omega-3 fatty acid-rich diet, can significantly delay mouse tumour growth when compared with a monounsaturated fatty acid-rich diet. Nevertheless, whether a combination of exercise, vitamin D and omega-3 fatty acids provides a synergistic and preventative effect against cancer is less clear.
For the present study, the researchers undertook a randomised controlled trial, which sought to examine the combination of exercise, supplementation with vitamin D and omega-3 fatty acids in older adults and how this impacted on the subsequent development of cancer. Their DO-HEALTH trial examined the combined effect of simple home strength exercise (SHEP), vitamin D (2000 IU/day) and/or 1g/day of marine omega-3 fatty acids, in healthy adults 70 years of age and older. For the primary outcome, the team considered the time to the development of a verified invasive cancer.
Combination of exercise, omega-3 fatty acids, vitamin D and cancer development
A total of 2157 individuals with a mean age of 74.9 years (61.7% female) were included in the study and followed for a median of 2.99 years. During this period of time there were 81 invasive cancers diagnosed and verified.
For the three separate interventions, the adjusted hazard ratios (compared to controls) were 0.76 (95% CI 0.49 – 1.18) for vitamin D, 0.70 (95% CI 0.44 – 1.09) for omega-3 fatty acids and 0.74 (95% CI 0.48 – 1.15) for SHEP). In other words, while there were beneficial effects from the individual interventions, the effects were not statistically significant, but when two of the interventions were combined, the effect did become statistically significant. For instance, the combination of SHEP and omega-3 resulted in an adjusted hazard ratio of 0.52 (95% CI 0.28 – 0.97, p = 0.039). However, the greatest benefit was derived from the combination of exercise, vitamin D and omega-3 fatty acids, with an adjusted hazard ratio of 0.39 (95% CI 0.18 – 0.85, p = 0.017).
The authors calculated that the number needed to treat to prevent one incident case of cancer after three years with the three treatments combined was 35.
They concluded that future studies should focus on the benefit of combining interventions as a means of cancer prevention.
Bischoff-Ferrari HA et al. Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial Am J Clin Nutr 2022
12th May 2022
A higher level of dairy consumption in Chinese adults has been found to be linked to an increased overall risk of developing cancer and in particular, liver and female breast cancers. This was the key finding of a prospective study by researchers from the UK and China.
Across the globe in 2020, it has been estimated that cancer was responsible for an estimated 19.3 million new cases and almost 10.0 million cancer deaths. Several dietary factors are linked with a reduced risk of developing cancer, including for example, a higher intake of fruit and vegetables, which is associated with a 17% lower cancer mortality. Another food linked with cancer is dairy products and a higher dairy consumption lowers the risk of developing colorectal cancer. However, intake of egg, fish and dairy consumption has remained at a low level among Chinese people with other work finding that dairy consumption was seriously inadequate in Chinese elderly and appears to be reducing. As a result, for the present study, researchers were interested in determining if, despite low levels of intake among the Chinese (compared to Westernised countries), dairy intake was associated with the incidence of cancer.
Turning to data held within the China Kadoorie Biobank, which represents a population-based prospective analysis with over 0.5 million adults across China, the researchers obtained information on the frequency of dairy consumption and which was categorised as daily, 4 – 6 day/week, 1 – 3 days/week, monthly or never/ready and which served as a baseline. The information on dairy intake was re-collected at two follow-up surveys and used to estimate mean intake of dairy foods. Cox regression analysis was used to link incident cancers with dairy consumption and adjusted for several covariates including a family history of cancer, alcohol intake and levels of smoking.
Dairy consumption and incident cancer
Among a population of 510,146 individuals with a mean age of 52 years (59% women), 20.4% reported intake of dairy foods at least once a week (subsequently referred to as ‘regular dairy consumers’) and which was largely for milk. Participants were followed for a mean of 10.8 years, during which time there were 29,277 incident cancer cases recorded. In the fully adjusted models, each 50g/day increase in dairy consumption was associated with a 7% increased risk of total cancer (hazard ratio, HR = 1.07, 95% CI 1.04 – 1.11) when compared to those who never consumed dairy foods. Furthermore, among regular dairy consumers, there was a significant increased risk of liver cancer (HR = 1.12, 95% CI 1.02 – 1.22) and for female breast cancer (HR = 1.17, 95% CI 1.07 – 1.29). There was no significant association for any other form of cancer including colorectal cancer.
The authors concluded that higher dairy consumption was associated with a greater risk of cancer among Chinese individuals even though levels of dairy intake are low compared to Westernised countries.
Kakkoura MG et al. Dairy consumption and risks of total and site-specific cancers in Chinese adults: an 11-year prospective study of 0.5 million people. BMC Med 2022
Cancer patients with COVID-19 have been found to be at a greater risk of hospitalisation and 30-day all-cause mortality compared to those without the disease according to the results of a study by a US team from Texas.
The presence of cancer has become a recognised factor that is associated with a higher risk for severe outcomes in those infected with COVID-19 and which is largely due to the presence of a compromised immune system. During the early course of the pandemic, studies observed that a higher proportion of cancer patients infected with COVID-19 were both hospitalised and subsequently died, compared to those without the disease. In contrast, however, other studies have suggested that cancer and non-cancer patients have comparable COVID-19 outcomes after adjusting for age, sex, and comorbidity. Furthermore, the impact of factors such as cancer treatments, different cancer types on COVID-19 related outcomes has been less well studied. For the present study, the US researchers examined the association between cancer-specific characteristics and COVID-19 outcomes. They turned to the Optum de-identified COVID-19 electronic health record, which is derived from over 700 hospitals and 7000 clinics across the USA. Using these data, the researchers examined the outcome of those with a laboratory confirmed COVID-19 and a recorded cancer diagnosis. The primary objective was to determine the effect of cancer on COVID-19 outcomes including 30-day all-cause mortality, hospitalisation, intensive care unit (ICU) admission and ventilator use. These outcomes were also analysed by the nature and type of cancer in comparison to patients without cancer. The authors the explored if there were any other specific factors in those with cancer which impacted on COVID-19 outcomes.
Cancer patient with COVID-19 and related outcomes
A total of 271,639 patients with confirmed COVID-19 of whom 18,460, with a mean age of 66 years (45.3% male) had a cancer diagnosis were analysed. Among those with cancer, 8034 patients had a history of cancer for longer than 12 months and 10,426 had a more recent diagnosis, i.e., within 1 year before COVID-19.
30-day all-cause mortality was more than three times higher among those with cancer (6.8% vs 1.9%) compared to non-cancer patients. After adjustment for age, sex, ethnicity and risk factors, the presence of cancer was associated with a 7% higher risk of death (relative risk, RR = 1.07, 95% CI 1.01 – 1.14, p = 0.028) compared to those without the disease. Similarly, there was a 4% higher risk of hospitalisation (RR = 1.04, 95% CI 1.01 – 1.07, p = 0.006). When comparing the duration of cancer, those with a recent diagnosis had both a significant (p < 0.001) increased risk of mortality (RR = 1.17) and hospitalisation (RR = 1.10) although this risk was non-significant for those who had cancer for much longer.
There was also an increased mortality risk for those with recent metastatic (RR = 2.09), solid tumour (RR = 1.12) and haematological (RR = 1.48) cancers compared with those without the disease. Individual cancers with a significantly elevated risk were leukaemia (RR = 1.58), liver (RR = 2.46), lung (RR = 1.85) and pancreatic (RR = 1.94).
When exploring the factors related to COVID-19 mortality in those with recent cancer, both chemotherapy (RR = 1.37) and radiotherapy (RR = 1.83) within 3-months before COVID-19, were significantly associated with a higher risk of death as was increasing age (i.e., > 75 years) (RR = 6.69). In addition, the only significant co-morbidities were cardiovascular disease (RR = 1.72), diabetes (RR = 1.39) and renal disease (RR = 1.51).
Kim Y et al. Characterizing cancer and COVID-19 outcomes using electronic health records PLoS One 2022
A higher body fat level in men is associated with an elevated risk of prostate cancer death according to a meta-analysis of prospective studies by researchers from the Nuffield Department of Population Health, Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide and in 2020 there were more than 1.4 million new cases of prostate cancer. Prior evidence indicates that there is a positive association between height and the risk of prostate cancer, with taller men being at a greater risk but also that those with greater adiposity, have an elevated risk of high-grade prostate cancer and prostate cancer death. Moreover, other work suggests that a higher body fat level, based on central adiposity is a more relevant factor and that a higher waist circumference was an important risk factor for prostate cancer.
For the present study, the Oxford team use data from the UK Biobank and focused on men who had originally undergone anthropometric measurements (e.g., height, weight, waist and hip circumference). A subgroup of these men also underwent abdominal MRI and a dual-energy X-ray absorptiometry (DXA) scan and for whom body mass index (BMI), waist and hip circumferences were re-assessed. The primary outcome of interest was prostate cancer as the underlying cause of death. In addition, the researchers combined their Biobank data with other published prospective studies to undertake a dose response meta-analysis.
Higher body fat levels and prostate cancer death
Among a cohort of 21,8237 men with a mean age at recruitment of 56.5 years, over a follow-up period of 11.6 years, 661 men (mean age = 63.1 years), died of prostate cancer.
In a multivariable-adjusted model, there was no statistically significant association of BMI, body fat percentage and waist circumference and prostate cancer mortality. However, for the waist to hip ratio (WHR), this association was significant per 0.05 unit increase (hazard ratio, HR = 1.07, 95% CI 1.01 – 1.14, P for trend = 0.028) when comparing the highest to lowest WHR quartiles.
In the meta-analysis, the hazard ratio was 1.10 (95% CI 1.07 – 1.12) for every 5kg/m2 increase in BMI, 1.03 for every 5% increase in body fat percentage, and 1.06 for every 0.05 increase in WHR.
Using the estimate for the effect of BMI from the meta-analysis, the authors estimated that as approximately 11,900 men died from prostate cancer each year (averaged between 2016 – 2018) and if their estimate was accurate, a reduction in mean BMI of 5kg/m2 would potentially lead to 1309 fewer prostate cancer deaths every year in the UK.
They concluded that men with higher body fat (both total and central) were at a higher risk of death from prostate cancer and that these findings provided a reason for men to maintain a healthy weight.
Perez‐Cornago A et al. Adiposity and risk of prostate cancer death: a prospective analysis in UK Biobank and meta-analysis of published studies BMC Med 2022
11th May 2022
A greater coffee consumption in those with type 2 diabetes is significantly associated with a reduction in the rate of decline in the estimated glomerular filtration rate (eGFR). This was the key finding from a prospective study by researchers from the Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Chronic kidney disease (CKD) is a non-communicable disease and which usually develops as a consequence of diabetes and hypertension. Disease severity in CKD can be assessed by a low serum creatinine-based eGFR, which indicates excretory kidney function and by a raised urinary albumin. Lifestyle management is deemed to be a fundamental aspect of diabetes care and this encompasses self-management education and support, medical nutrition therapy, physical activity, smoking cessation counselling and psychosocial care. Nutritional therapy, however, does not just include what foods to eat but also what should be drunk. One commonly consumed beverage is coffee and a higher coffee consumption, as well as green tea, has been found to be associated with a reduction in all-cause mortality, particularly in patients with type 2 diabetes. Furthermore, some data suggests that a higher coffee consumption is associated with lower risk for incident CKD. Nevertheless, this finding is not consistent, with other work undertaken in men, find that there was no significant association between coffee consumption and CKD.
What remains unclear though, is if a higher level of coffee consumption in patients with type 2 diabetes would reduce the decline in kidney function. For the present study, the Japanese team carried out a prospective study of adult diabetic patients attending diabetic clinics throughout the country. They carried out a dietary survey which asked about coffee consumption but also had access to clinical measurements such as blood pressure and eGFR taken at the clinics. Coffee consumption was recorded as none, less than 1 cup/day, one cup/day or two or more cups/day. The primary outcome was set as a decline in eGFR to <60 mL/min/ 1.73 m2, based on two consecutive measures of eGFR during the follow-up period.
Coffee consumption and decline in eGFR rate
In total, 3,805 patients with type 2 diabetes and a mean age of 64.2 years (44.4% female) and eGFR ≥60ml/min/1.73 m2 were followed-up for a median of 5.3 years.
During the period of follow-up, 840 participants experienced a decline in eGFR of < 60 mL/min/1.73 m2. Using multivariate analysis, the researched found that compared to those who drank no coffee, the adjusted hazard ratio (aHR) for a decline in eGFR associated with drinking less than one cup/day was 0.77 (95% CI 0.63 – 0.97) and this increased slightly to 0.75 (95% CI 0.62 – 0.91) for those drinking two or more cups/day.
The mean eGFR change per year was -2.16ml/min/1.73 m2 with no coffee consumption, and -1.78ml/min/1.73 m2 with two or more cups per day (p for trend 0.03).
There was also no significant effect on coffee drinking and the decline in eGFR based on age, gender, body mass index, smoking status, those who exercised regularly or blood pressure.
The authors concluded that coffee consumption is significantly associated with a lower risk of a decline in eGFR, which suggested a progressive impairment in renal function, in patients with type 2 diabetes.
Komorita Y et al. Relationship of coffee consumption with a decline in kidney function among patients with type 2 diabetes: The Fukuoka Diabetes Registry J Diabetes Investig 2022
9th May 2022
Adult asthmatics and, in particular individuals who have had the disease for a long period of time and use oral corticosteroids, have been found to have a small, but significantly increased risk of developing obesity compared with those without the disease. This was the main finding of a study by researchers from the Division of Pulmonary Medicine, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Canada.
Data for 2016 shows that more than 1.9 billion adults were overweight and, of these, over 650 million were obese. It has also been found that while obese people report more incident asthma, it is not clear whether this represents reactivation of previously diagnosed asthma or the onset of new cases. Nevertheless, data for children are much clearer with one study finding that among asthmatics, there is a 51% increased risk of developing obesity during childhood and adolescence compared to children without asthma.
Since the relationship between asthma and obesity in adults remains unclear, in the present study, the researchers sought to investigate the occurrence of obesity due to asthma among participants in the European Community Respiratory Health Survey (ECRHS) over 2 periods of 10 years, which were labelled ECRHS-II and ECRHS-III. ECRHS-I began in 1990 and recruited over 18,000 participants and had two follow-up periods at approximately 10-year intervals. The researchers excluded those with a diagnosis of obesity at baseline and then classified individuals as either having ‘no asthma’ or ‘current asthma’. Additional data on the duration of asthma, treatments used and the presence or absence of atopy (based on serum levels of IgE to common allergens) was also collected.
Adult asthmatics and the risk of obesity
The research team included 7576 participants with a baseline mean age of 34 years (51.5% female) in ECRHS I-II and 4976 participants (mean age 42, 51.3% female) in ECRHS-II-III.
The risk of developing obesity was higher among asthmatics compared to those without the condition (relative risk, RR = 1.22, 95% CI 1.07 – 1.38). Furthermore, this risk was also higher among those without atopy (RR = 1.47), for individuals who had asthma for longer than 20 years (RR = 1.32, 95% CI 1.10 – 1.59) and for those using oral corticosteroids (RR = 1.99, 95% CI 1.26 – 3.15). In subgroup analysis, smokers also had a higher risk of becoming obese compared to non-smokers (RR = 1.46).
The authors concluded that adult asthmatics were at a greater risk of developing obesity in later life, especially those with longstanding disease, who were using oral corticosteroids and had non-atopic asthma.
Moitra S et al. Long-term effect of asthma on the development of obesity among adults: an international cohort study, ECRHS Thorax 2022
The use of a fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet has been shown in a randomised controlled trial to provide much better relief of irritable bowel syndrome (IBS) symptoms compared with using a musculotropic spasmolytic agent. This was the main result from a study by researchers at the department of Gastroenterology and Hepatology, KU Leuven University Hospitals Leuven, Belgium.
Irritable bowel syndrome has been defined as a functional bowel disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits. It is a common condition and in one 2020 review, the pooled IBS prevalence among studies that used the Rome IV criteria was 3·8%. Several treatment options are available for the management of IBS and a 2008 systemic review and meta-analysis concluded that fibre, anti-spasmodics (musculotropic spasmolytics) and peppermint oil were all more effective than placebo in the treatment of IBS. One particular spasmolytic agent is otilonium bromide (OB) which acts as an L-type calcium channel antagonist in intestinal and colonic smooth muscle cells. OB has been found to be more effective than placebo in IBS with a significant therapeutic benefit after 10 weeks and which is maximal after 15 weeks. In recent years however, the use of a FODMAP diet has been found to be effective at reducing functional gastrointestinal symptoms in patients with IBS. Nevertheless, there is uncertainty over whether or not a FODMAP diet provides superior symptomatic relief for patients with IBS compared to the use OB.
For the current trial, the Belgium team randomised newly treated patients with IBS to either OB 40mg three-times daily or a FODMAP diet and which was made available via a smartphone app and for those without access to a suitable electronic device, the diet instructions were available as a booklet. The diet itself was not a strict low FODMAP diet, but rather designed as a FODMAP-lowering diet. Consequently, small amount of FODMAPs were allowed, but the app did provide advice on which foods should be avoided or be reduced and offered suitable alternatives. Patients self-completed several questionnaires, one of which was the IBS symptom Severity scale (IBS-SSS) and this used for the primary outcome, with a responder defined as a patient who improved by ≥50 points on the IBS-SSS compared with baseline after 8 weeks.
FODMAP and improvement in IBS symptom scores
A total of 459 patients were randomised to OB (232) or a FODMAP diet. The mean age of participants randomised to OB was 41.2 years (76% female) which was slightly higher than the mean age of those assigned to the diet (40.6 years). The mean baseline IBS-SSS score was the same (267) in both groups.
After 8 weeks, a significantly higher proportion of participants using the FODMAP diet arm achieved the primary outcome (71% vs 61%, diet vs OD, p = 0.03). In fact, this difference became significant after only 4 weeks (62% vs 51%, diet vs OB, p = 0.02). Numerically, FODMAP diet participants saw a change from baseline in their IBS-SSS score of -97.42 after 8 weeks whereas the OB experienced a smaller mean reduction of only -76.91.
The authors concluded that the FODMAP diet was superior to standard medical therapy and suggested that this simple dietary approach should be considered as a first-line therapy for patients with IBS.
Carbone F et al. Diet or medication in primary care patients with IBS: the DOMINO study – a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute Gut 2022
In a press release from the manufacturer, Lilly, headline results from a trial have shown that use of the anti-diabetic agent tirzepatide 15 mg for 72 weeks in a Phase III randomised trial, led to a 22.5% reduction in weight among those classed as either overweight and obese patients.
Tirzepatide is described as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is in development for the treatment of type 2 diabetes. Early data from studies in mice suggested that chronic administration of the drug, could reduce both food intake and body weight and how it was suitable for administration on a weekly basis. Moreover, studies in humans have shown the drug to be an effective treatment for patients with type 2 diabetes. For example, in randomised, double-blind phase 3 trial in patients with type 2 diabetes, tirzepatide was found to produce significantly better efficacy with regard to glucose control and weight loss than the comparator, dulaglutide. In addition, in an open-label, 40-week trial, in 1879 patients with type 2 diabetes, tirzepatide was found to be non-inferior and superior to semaglutide with respect to the mean change in the glycated haemoglobin level from baseline to 40 weeks.
Tirzepatide and weight loss
Although the evidence points to tirzepatide being an effective treatment for type 2 diabetes, for the current press release, the manufacturer focused on the results from the SURMOUNT-1 trial in which the drug was administered to overweight or obese patients without type 2 diabetes, with a mean baseline body weight of 105 kg.
The SURMOUNT-1 trial randomised 2,539 participants in a 1:1:1:1 ratio to different doses of tirzepatide (5mg, 10mg or 15mg) or placebo and the treatment was given as an adjunct to a reduced-calorie diet combined with increased physical activity. All of the participants receiving tirzepatide were started at a dose of tirzepatide 2.5mg once-weekly and then increased in a step-wise approach at four-week intervals to their final randomised maintenance doses. The co-primary endpoints of the study were to show that tirzepatide 10mg and/or 15 mg were superior to placebo in the percentage reduction in body weight compared with baseline and the percentage of participants who achieved a ≥5% body weight reduction at 72 weeks, again compared with placebo.
At the end of the trial, among those taking tirzepatide, average weight reductions were 16.0% (5mg), 21.4% (10mg) and 22.5% (15mg), compared with 2.4% in the placebo arm. Furthermore, the proportion of participants achieving a body weight reduction of ≥5% were 85% (5mg), 89% (10mg), 91% (15mg), and 35% (placebo).
The press release also demonstrates how tirzepatide was well tolerated with the most commonly reported adverse events being gastrointestinal-related and generally mild to moderate in severity, usually occurring during the dose escalation period. Adverse effects included nausea, diarrhoea, vomiting and constipation which were more frequently experienced compared to placebo. In fact, the overall treatment discontinuation rates due to adverse events were 14.3% (5mg), 16.4% (10mg), 15.1% (15mg) and 26.4% (placebo).
The company is also currently undertaking further trials in overweight patients with type 2 diabetes.
6th May 2022
Use of an AI-based breast cancer protocol has been found to have a similar screening sensitivity and a slightly higher specificity than radiologists and might therefore be able to considerably reduce the workload of radiologists. This was the finding from a retrospective analysis by researchers from the Department of Computer Science and Public Health, University of Copenhagen, Copenhagen, Denmark.
Breast cancer arises in the epithelium of the ducts or lobules in the glandular tissue of the breast and according to the World Health Organization, in 2020 there were 2.3 million women diagnosed with breast cancer and 685 000 global deaths. Population screening of women enables the detection of the early signs of breast cancer and one European analysis of observational studies concluded that the estimated breast cancer mortality reduction from invited screening was 25-31% and 38-48% for women actually screened. Although screening mammography is the principle method for the detection of breast cancer, 10%-30% of breast cancers may be missed at mammography. Part of the reason for missing possible cancers may be due to behavioural factors. For example, in one study, six radiologists who reviewed 100 breast cancer scans, where the prevalence of disease was artificially set at 50%, missed 30% of the cancers. In contrast, when the prevalence was raised, participants missed just 12% of the same cancers. In other words, radiologists are more likely to be on the look-out of suspicious scans when they know that the disease has a much higher prevalence.
One potential way to remove the effect of behavioural influences is the use of an artificial intelligence (AI) based system for reading breast cancer scans. In fact, such systems have been shown to maintain non-inferior performance and reduced the workload of the second, radiologist reader by 88%. But whether an AI-based breast cancer system could be safely used for population-based screening and reduce the number of mammograms that required reading by a radiologist is uncertain and was the objective of the current study. Using a retrospective design, the Danish researchers examined whether the AI-based cancer protocol was able to detect normal, moderate-risk and suspicious mammograms. The team used data from a breast cancer screening program and each of the mammograms was scored from 0 to 10 (to designate the risk of malignancy) by the AI-based cancer tool. The team then compared to AI-based cancer system and radiologists with respect to screening performance and used the area under the receiver operating characteristics curve (AUC) to compare performance.
AI-based cancer screening protocol performance
The cohort included 114,421 women with a mean age of 59 years who underwent mammography screening. The scanning identified 791 screen-detected cancers, 327 interval cancers and 1473 long-term cancers.
The AI-based cancer system had a screening sensitivity of 69.7% (95% CI 66.9 – 72.4%) which was non-inferior to the radiologist sensitivity of 70.8% (p = 0.02). The AI-based screening specificity was 98.6% and which was significantly higher (p < 0.001) than that of the radiologist (98.1%).
Based on these findings, the authors calculated that use of the AI-based cancer system led to a 62.6% radiologist workload reduction. Moreover, the AI-based system reduced the number of false-positive screenings by 25.1%.
They concluded that incorporation of an AI-based cancer system for population-based screening could both improve these programs and reduce radiologist workload and called for a prospective trial to determine the impact of AI-based screening.
Lauritzen AD et al. An Artificial Intelligence–based Mammography Screening Protocol for Breast Cancer: Outcome and Radiologist Workload Radiology 2022