2 Minute Medicine Rewind March 3, 2025
Physical health decline after chemotherapy or endocrine therapy in breast cancer survivors
1. In this cohort comparing physical health outcomes among women, those with breast cancer (BC) who received chemotherapy with or without endocrine therapy had a decline in physical health up to 5 years post-diagnosis compared to women without BC.
Evidence Rating Level: 1 (Excellent)
Throughout the years, the number of women in the United States with a history of breast cancer (BC) has been increasing and is estimated to rise further. Fortunately, there is good treatment for early-stage breast cancer, so the 5-year relative survival has also risen to around 90%. Along with increased survival time comes increased time to develop complications from the treatment. Depending on the characteristics of the BC, the treatment method is different. Most types of BC are treated with endocrine therapy which acts by suppressing transcription of estrogen responsive genes or inhibiting estrogen production. Whereas other types of BC are treated with radiation or chemotherapy, which causes DNA damage leading to cell death. Thus, the effects on aging might differ between the two treatment types. To understand the differing effects of this treatment on health outcomes, a prospective cohort study was conducted with women diagnosed with BC. Individuals were eligible to participate if they were between the ages of 30 and 65 with no personal history of cancer. Physical health of the participants was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health version with lower scores indicating worse physical health. A total of 15,392 women (median (IQR) age was 56.3 (49.9-61.9) years) were included in the study, with 2566 of those being diagnosed with BC and 12,826 matched women without BC. In the women with BC, 433 (16.9%) did not receive any treatment, 1223 (47.7%) received endocrine treatment, 276 (10.8%) received chemotherapy, and 634 (24.7%) received both endocrine treatment and chemotherapy. There was a greater physical health decline in the first 2 years of BC diagnosis in women who received endocrine therapy (β=-1.12; 95% CI, -1.64 to -0.60), chemotherapy (β=-3.13; 95% CI, -4.19 to 2.07), or both treatments (β=-3.26; 95% CI, -3.7 to -2.55) compared to matched women without cancer. Amongst the women who received endocrine therapy, the decline was only observable in those using aromatase inhibitors. noticeable decline was observed only in women who received chemotherapy more than 2 years after their diagnosis. In summary, there was a greater physical health decline in women with BC compared to matched women without in the 2 years following their diagnosis. Specifically, the greatest decline was seen in women who received chemotherapy.
Race and Ethnicity, Lifestyle, Diet, and Survival in Patients With Prostate Cancer
1. In this prospective cohort of multiethnic men diagnosed with nonmetastatic prostate cancer (PCa), maintaining a healthier lifestyle post-diagnosis was associated with a lower risk of mortality compared to men with poorer lifestyle patterns.
Evidence Rating Level: 1 (Excellent)
Prostate cancer (PCa) is one of the leading causes of cancer-related death among men in the United States. Previous studies on postdiagnosis modifiable factors and their impact on PCa continue to yield inconclusive results. Among these factors, postdiagnosis physical activity has been associated with benefit, while smoking, and high-fat dairy intake have been associated with increased mortality. Other studies have evaluated the influence of specific dietary patterns on health outcomes, however, these have not included diverse populations. This study aimed to determine the associations between lifestyle and dietary scores and risk of PCa, cardiovascular disease (CVD), and overall mortality in multiethnic men with PCa. The participants filled out a self-administered questionnaire providing data on their demographics, and a quantitative food frequency questionnaire providing baseline dietary habits. Similarly, to assess lifestyle patterns postdiagnosis, the PCa Behavior Score was used. Individuals were excluded from the study if they had metastatic disease, missing stage or grade information, or incomplete data. The four dietary indices included were the HEI-2025 (Healthy Eating Index), Healthful Plant-Based Diet Index (hPDI), Energy-Adjusted Dietary Inflammatory Index (E-DII), and the Empirical Dietary Index for Hyperinsulinemia (EDIH). After meeting eligibility criteria, 2603 men were included (mean [SD] age, 69.6 [7.1] years). Among the participants there were a total of 1346 deaths, of which 197 (14.6%) were due to PCa. For each 1-point increase in score there was an associated reduction in all-cause mortality (HR per point, 0.69; 95% CI, 0.63-0.77) and CVD-related mortality (HR, 0.67; 95% CI, 0.56-0.79). Comparing the highest score (quintile 5) with the lowest score (quintile 1), there was an inverse association between better HEI-2025 adherence (HR, 0.74; 95% CI, 0.56-0.99) (P=.02) or hPDI (HR, 0.75; 95% CI, 0.58-0.97) (P=.03), and all-cause mortality. When the results were stratified by racial group, there was a significantly lower risk of PCa-specific mortality associated with the 2021 score among African Americans but no other racial or ethnic group (P for heterogeneity=.04). Overall, in this prospective cohort study, men with PCa who had better lifestyle patterns, including dietary patterns, had a lower risk of mortality.
1. In this new-user cohort study, glucagon-like peptide-1 (GLP-1) receptor agonists were not associated with an increased risk of suicidality compared to dipeptidyl peptidase-4 (DPP-4) inhibitors or sodium-glucose cotransporter-2 (SGLT-2) inhibitors.
Evidence Rating Level: 2 (Good)
The glucagon-like peptide-1 (GLP-1) receptor agonist drug class is widely prescribed to manage type 2 diabetes, due to its highly effective glycemic control. However, despite the benefits, recent studies have linked GLP-1 receptor agonists to self-harm and suicidal ideation. These studies did not reach definitive conclusions as to the mechanism that causes those thoughts. Due to more widespread use of GLP-1 receptor agonists, an observational study was done comparing them with continuous dipeptidyl peptidase-4 (DPP-4) inhibitor or sodium-glucose cotransporter-2 (SGLT-2) inhibitor use on suicidal ideation, self-harm, and suicide among patients with type-2 diabetes. Data was drawn from the UK Clinical Practice Research Datalink (CPRD) GOLD and Aurum, with patients divided into 2 cohorts: one consisting of patients on GLP-1 receptor agonist or DPP-4 inhibitor, and the second consisting of patients on GLP-1 receptor agonist or an SGLT-2 inhibitor. Patients were compared on each drug by suicidal ideation, hospital admission for self-harm, and completed suicide. Potential cofounders included age, sex, BMI, severe diabetes, mental health disorders, and other suicidality variables. These factors were accounted for through propensity score fine stratification weighting. The first cohort was comprised of 36 082 and 234 028 new users of GLP-1 receptor agonists and DPP-4 inhibitors respectively. A total of 301 suicide events occurred over 77 377 person years in users of GLP-1 agonists, while 1087 events occurred over 599 271 person years among DPP-4 inhibitor users, however, after weighting, did not represent an elevated hazard risk (weighted incidence rate 3.9 (95% CI 3.5 to 4.4) v 3.7 (3.6 to 3.9) per 1000 person years, respectively; weighted hazard ratio 1.02, 0.85 to 1.23). The second cohort consisted of 32 336 GLP-1 receptor agonist users and 96 212 SGLT-2 inhibitor users respectively. A total of 240 suicidality events were recorded over 55620 person years for GLP-1 users while 454 events were recorded over 168384 person years for SGLT-2 users. The hazard ratio was null after adjusting for confounding factors (weighted incidence rate 4.3 (95% CI 3.8 to 4.9) v 4.6 (4.3 to 4.9), respectively; weighted hazard ratio 0.91, 0.73 to 1.12). Some strengths of the study included being able to adjust for cofounders, due to the depth of the database, however, potential residual confounding is a major limitation. Overall, the study found that GLP-1 receptor agonists did not show increased risk of suicidality compared to DPP-4 and SGLT-2 in type-2 diabetics.
1. In a cohort of children with type 1 diabetes mellitus (T1DM) Acute kidney injury (AKI) presenting at T1DM onset was associated with decreased peripheral sensitivity and increased central sensitivity.
Evidence Rating Level: 1 (Excellent)
Type 1 diabetes mellitus (T1DM) often initially presents with complications of diabetic ketoacidosis (DKA) and acute kidney injury (AKI). AKI affects 65% of patients at type 1 diabetes mellitus (T1DM) onset, which risks development of chronic kidney disease (CKD). This study aims to examine the link between thyroid function and kidney function, specifically the impact of thyroid hormones (TH) sensitivity. As euthyroid sickness syndrome (ESS) has shown impact of AKI at T1DM onset, it is thought that TH sensitivity could play a role in causing AKI. The study aimed to analyze the relationship between TH sensitivity in children and AKI at T1DM onset, as well as the impact ESS had on the AKI and TH sensitivity relationship. The 161 patients in the cohort had T1DM before the age of 18, of which 73 (45.3%) had AKI at the onset. Additionally, in 60 (37.3%) patients ESS was identified. Patients with AKI had higher prevalence of ESS as well as lower TH ratios. The patients with ESS further displayed lower TH ratios compared to those without. These adjusted ratios indicated a higher TH sensitivity or more pronounced feedback to adjustments in TH, however, the reverse was shown at the peripheral level, shown by FT3/FT4 ratios, hypothesized to be a protective adaptation to reduce oxidative stress and energy consumption. The associations seem to stem from ESS, which is characterized by altered TH metabolism during illness without underlying thyroid dysfunction. These conditions all resolved within participants, indicating minimal need for treating the thyroid dysfunction, instead showing greater severity of T1DM onset. A limitation of the study was the single-center enrollment, which reduced the sample size, and limited generalizability. Overall, AKI at T1DM onset decreased peripheral TH sensitivity while increasing central sensitivity, with future research needed on long-term effects on kidney function.
Antidepressant use and cognitive decline in patients with dementia: a national cohort study
1. In a cohort of patients with dementia, antidepressant usage was associated with faster cognitive decline, particularly some selective serotonin reuptake inhibitors (SSRIs) and mirtazapine.
2. Greater antidepressant usage (greater dispensed doses) was associated with increased risk of fractures, and all-cause mortality.
Evidence Rating Level: 2 (Good)
Dementia is often accompanied by neuropsychiatric symptoms such as anxiety and depression, which can be treated with antidepressants. The first line antidepressants used are selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) due to their decreased side effect profile. However, the efficacy of antidepressants on dementia progression remains unclear. Furthermore, antidepressants have been shown to not work as well in those with dementia and the effectiveness of some SSRIs gets reduced by cognitive control dysfunction. The goal of this study was to understand the long-term effects of antidepressants on cognitive decline and mortality in patients with dementia. To best complete this, a population-based cohort study included patients with incident dementia. The Mini-Mental State Examination (MMSE) scores helped distinguish severity of dementia. To clinically diagnose dementia disorders, the International Classification of Diseases, Tenth Revision (ICD-10) codes were used. Types of dementia included Alzheimer’s disease (AD), vascular dementia (VaD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and other dementias. The primary outcome was cognitive decline was the secondary outcomes included severe dementia (MMSE<10), fractures, and mortality. A total of 18,740 patients (mean [SD] age, 78.2 (7.4) and MMSE score 22.1 (4.3)) were included. Of these patients, a minimum of 4271 (22.8%) received at least one prescription for an antidepressant, with a total of 11,912 prescriptions issued. Antidepressant use was associated with faster cognitive decline (β=-0.30 points/year; 95% CI, -0.39 to -0.21) compared to non-use. Specifically, sertraline (β=-0.41 points/year; 95% CI, -0.43 to -0.06), citalopram (β=-0.41 points/year; 95% CI, -0.55 to -0.27), escitalopram (β=-0.76 points/year; 95% CI, -1.09 to -0.44) and mirtazapine (β=-0.19 points/year; 95% CI, -0.34 to -0.04) all led to faster cognitive decline compared to no antidepressant use. This association was more pronounced in patients with severe dementia. Citalopram was associated with a slower cognitive decline and escitalopram with a faster cognitive decline compared to sertraline. Antidepressant use was associated with increased risk of fractures (HR=1.18; 95% CI, 1.10 to 1.26) and all-cause mortality (HR=1.07; 95% CI, 1.01 to 1.13) compared with non-use. In this cohort study of individuals with dementia, the use of antidepressants was associated with faster cognitive decline compared with non-use.
Image: PD
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