Giuseppe Bellelli, Maria Cristina Ferrara, Federico Triolo, Davide Liborio Vetrano
<p>Dear Editor,</p><p>We thank Drs. da Silva and Caldas for showing interest in our review paper recently published in the <i>Journal of Internal Medicine</i> and for their thoughtful contributions, which enrich the discussion on this topic [<span>1, 2</span>].</p><p>A highlighted key point pertains to the pathophysiology of frailty and delirium. As acknowledged, the biological mechanisms underlying these two conditions remain largely unknown. This limited understanding explains why current prevention and treatment strategies predominantly focus on minimizing observable clinical manifestations (i.e., secondary rather than primary prevention). From a biological perspective, identifying whether certain individuals have an increased susceptibility to develop frailty and delirium remains a key challenge. This underscores the urgent need for a paradigm shift in our approach to these conditions.</p><p>In our review, we proposed a unifying framework aimed at offering a novel reading of the complex pathophysiological mechanisms underlying these conditions and, most importantly, providing research perspectives for future etiological studies. While recognizing frailty and delirium as distinct clinical entities, we postulated that they may reflect different manifestations of accelerated biological aging. This viewpoint opens new avenues from a geroscience perspective, particularly in identifying individuals at higher risk of developing delirium when frail or presenting with worsening frailty status after a delirium episode. Additionally, exploring upstream interventions targeting shared biological mechanisms holds significant promise for mitigating both conditions, as well as other burdensome geriatric syndromes. Advancing this line of research could lead to breakthroughs in risk stratification and the development of early, personalized interventions, ultimately improving care outcomes for older adults.</p><p>The letter by da Silva and Caldas also raises the critical issue of cognitive decline underdiagnosis, which we fully acknowledge. Cognitive impairment often goes unnoticed, either because healthcare access is strongly influenced by one's socioeconomic status or because healthcare providers often lack the necessary training to identify it. Expanding awareness among healthcare professionals about the interplay among frailty, delirium, and cognitive decline is essential to enhance prevention efforts and foster a more integrated, multidisciplinary approach to the care of, among others, at-risk hospitalized older adults. Equally important is educating communities to recognize cognitive decline as a serious issue that impacts the quality of care for older individuals.</p><p>Although our review is not systematic, we believe that its narrative approach offers valuable insights by synthesizing fragmented evidence and generating hypotheses for future studies. Addressing the identified gaps will enable healthcare systems and caregivers to implement interventions
{"title":"Authors reply: Delirium and frailty in older adults: Clinical overlap and biological underpinnings","authors":"Giuseppe Bellelli, Maria Cristina Ferrara, Federico Triolo, Davide Liborio Vetrano","doi":"10.1111/joim.20047","DOIUrl":"10.1111/joim.20047","url":null,"abstract":"<p>Dear Editor,</p><p>We thank Drs. da Silva and Caldas for showing interest in our review paper recently published in the <i>Journal of Internal Medicine</i> and for their thoughtful contributions, which enrich the discussion on this topic [<span>1, 2</span>].</p><p>A highlighted key point pertains to the pathophysiology of frailty and delirium. As acknowledged, the biological mechanisms underlying these two conditions remain largely unknown. This limited understanding explains why current prevention and treatment strategies predominantly focus on minimizing observable clinical manifestations (i.e., secondary rather than primary prevention). From a biological perspective, identifying whether certain individuals have an increased susceptibility to develop frailty and delirium remains a key challenge. This underscores the urgent need for a paradigm shift in our approach to these conditions.</p><p>In our review, we proposed a unifying framework aimed at offering a novel reading of the complex pathophysiological mechanisms underlying these conditions and, most importantly, providing research perspectives for future etiological studies. While recognizing frailty and delirium as distinct clinical entities, we postulated that they may reflect different manifestations of accelerated biological aging. This viewpoint opens new avenues from a geroscience perspective, particularly in identifying individuals at higher risk of developing delirium when frail or presenting with worsening frailty status after a delirium episode. Additionally, exploring upstream interventions targeting shared biological mechanisms holds significant promise for mitigating both conditions, as well as other burdensome geriatric syndromes. Advancing this line of research could lead to breakthroughs in risk stratification and the development of early, personalized interventions, ultimately improving care outcomes for older adults.</p><p>The letter by da Silva and Caldas also raises the critical issue of cognitive decline underdiagnosis, which we fully acknowledge. Cognitive impairment often goes unnoticed, either because healthcare access is strongly influenced by one's socioeconomic status or because healthcare providers often lack the necessary training to identify it. Expanding awareness among healthcare professionals about the interplay among frailty, delirium, and cognitive decline is essential to enhance prevention efforts and foster a more integrated, multidisciplinary approach to the care of, among others, at-risk hospitalized older adults. Equally important is educating communities to recognize cognitive decline as a serious issue that impacts the quality of care for older individuals.</p><p>Although our review is not systematic, we believe that its narrative approach offers valuable insights by synthesizing fragmented evidence and generating hypotheses for future studies. Addressing the identified gaps will enable healthcare systems and caregivers to implement interventions ","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 2","pages":"232-233"},"PeriodicalIF":9.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jung-Joon Cha, Ju Hyeon Kim, Soon Jun Hong, Subin Lim, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Pil Hyung Lee, Seung Whan Lee, Cheol Whan Lee, Jae Youn Moon, Jong-Young Lee, Jung-Sun Kim, Jae Suk Park, Do-Sun Lim
Background: High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins.
Objective: To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy.
Method: In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70 mg/dL) within 6 months.
Results: The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p = 0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels.
Conclusion: Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.
{"title":"Safety and efficacy of moderate-intensity statin with ezetimibe in elderly patients with atherosclerotic cardiovascular disease.","authors":"Jung-Joon Cha, Ju Hyeon Kim, Soon Jun Hong, Subin Lim, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Pil Hyung Lee, Seung Whan Lee, Cheol Whan Lee, Jae Youn Moon, Jong-Young Lee, Jung-Sun Kim, Jae Suk Park, Do-Sun Lim","doi":"10.1111/joim.20029","DOIUrl":"https://doi.org/10.1111/joim.20029","url":null,"abstract":"<p><strong>Background: </strong>High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins.</p><p><strong>Objective: </strong>To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy.</p><p><strong>Method: </strong>In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70 mg/dL) within 6 months.</p><p><strong>Results: </strong>The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p = 0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels.</p><p><strong>Conclusion: </strong>Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.</p>","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The interplay of delirium and frailty in hospitalized older adults: Implications for healthcare utilization","authors":"Zhiying Lim, Natalie Ling, Reshma Aziz Merchant","doi":"10.1111/joim.20046","DOIUrl":"10.1111/joim.20046","url":null,"abstract":"","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 2","pages":"227-229"},"PeriodicalIF":9.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>It is well known that overconsumption of alcohol can cause tissue injury in the liver and the pancreas, apart from many other organs such as the heart, brain, and peripheral nervous system. It has also been recognized that less than 5% of individuals who drink excessively will develop episodes of acute pancreatitis [<span>1</span>]. The definition of heavy drinking is beyond the scope of this editorial, and obtaining a reliable history of alcohol use can be a challenge. The pattern of use and the lifetime drinking history did not reveal any major differences among patients with alcohol use disorder (AUD) who were hospitalized for alcohol rehabilitation (without a history of alcoholic pancreatitis) and patients previously diagnosed with alcohol-induced pancreatitis (AIP) [<span>2</span>]. In that study, males with AIP had a significantly lower total amount of spirits and a lower proportion of binge drinking than those with AUD, suggesting the <i>idiosyncratic</i> etiology of AIP [<span>2</span>]. In a study from Portugal, lifestyle and eating habits seemed to impact the development of alcoholic pancreatitis [<span>3</span>]. Patients with alcoholic liver disease (ALD) had significantly higher alcohol consumption than AIP patients, and the latter group reported a more abundant diet in the past [<span>3</span>]. A Swedish prospective and population-based study revealed that vegetable but not fruit consumption might prevent the development of non-gallstone-related acute pancreatitis [<span>4</span>]. Thus, lifestyle and diet may influence the development of AIP apart from alcohol consumption [<span>2-4</span>]. Although more knowledge is available on the risk of ALD based on threshold values of alcohol consumption, only a minority of heavy drinkers develop ALD [<span>5</span>]. However, the incidence of both ALD and AIP has been shown to increase with increased per capita alcohol consumption in the general population [<span>6</span>].</p><p>In the present issue of the Journal of Internal Medicine, Dugic et al. reported a sixfold increase in AIP in patients with ALD compared to matched controls [<span>7</span>]. A total of 7% of the patients had experienced pancreatitis prior to the diagnosis of ALD, suggesting a ninefold higher risk compared with the matched controls. However, the cumulative incidence of hospitalization for AIP in patients with ALP was only 2.7% [<span>7</span>]. Although the risk was higher than in matched controls, the risk seems very low that ALD patients will suffer from AIP. In the study by Dugic et al., independent risk factors for developing AIP were younger age, male sex, and diagnoses of alcohol and obstructive pulmonary disease [<span>7</span>].</p><p>The study included an impressive number of patients diagnosed with ALD, and the study has a long follow-up. This was a registry study from good quality health care in Sweden and a socialized medicine system, which means that all patients hospitalized for ALD in Sweden durin
{"title":"Alcohol-induced pancreatitis and alcohol-related liver disease: Two different phenotypes of alcohol-related harm or related conditions?","authors":"Einar Stefan Björnsson","doi":"10.1111/joim.20043","DOIUrl":"10.1111/joim.20043","url":null,"abstract":"<p>It is well known that overconsumption of alcohol can cause tissue injury in the liver and the pancreas, apart from many other organs such as the heart, brain, and peripheral nervous system. It has also been recognized that less than 5% of individuals who drink excessively will develop episodes of acute pancreatitis [<span>1</span>]. The definition of heavy drinking is beyond the scope of this editorial, and obtaining a reliable history of alcohol use can be a challenge. The pattern of use and the lifetime drinking history did not reveal any major differences among patients with alcohol use disorder (AUD) who were hospitalized for alcohol rehabilitation (without a history of alcoholic pancreatitis) and patients previously diagnosed with alcohol-induced pancreatitis (AIP) [<span>2</span>]. In that study, males with AIP had a significantly lower total amount of spirits and a lower proportion of binge drinking than those with AUD, suggesting the <i>idiosyncratic</i> etiology of AIP [<span>2</span>]. In a study from Portugal, lifestyle and eating habits seemed to impact the development of alcoholic pancreatitis [<span>3</span>]. Patients with alcoholic liver disease (ALD) had significantly higher alcohol consumption than AIP patients, and the latter group reported a more abundant diet in the past [<span>3</span>]. A Swedish prospective and population-based study revealed that vegetable but not fruit consumption might prevent the development of non-gallstone-related acute pancreatitis [<span>4</span>]. Thus, lifestyle and diet may influence the development of AIP apart from alcohol consumption [<span>2-4</span>]. Although more knowledge is available on the risk of ALD based on threshold values of alcohol consumption, only a minority of heavy drinkers develop ALD [<span>5</span>]. However, the incidence of both ALD and AIP has been shown to increase with increased per capita alcohol consumption in the general population [<span>6</span>].</p><p>In the present issue of the Journal of Internal Medicine, Dugic et al. reported a sixfold increase in AIP in patients with ALD compared to matched controls [<span>7</span>]. A total of 7% of the patients had experienced pancreatitis prior to the diagnosis of ALD, suggesting a ninefold higher risk compared with the matched controls. However, the cumulative incidence of hospitalization for AIP in patients with ALP was only 2.7% [<span>7</span>]. Although the risk was higher than in matched controls, the risk seems very low that ALD patients will suffer from AIP. In the study by Dugic et al., independent risk factors for developing AIP were younger age, male sex, and diagnoses of alcohol and obstructive pulmonary disease [<span>7</span>].</p><p>The study included an impressive number of patients diagnosed with ALD, and the study has a long follow-up. This was a registry study from good quality health care in Sweden and a socialized medicine system, which means that all patients hospitalized for ALD in Sweden durin","PeriodicalId":196,"journal":{"name":"Journal of Internal Medicine","volume":"297 2","pages":"122-123"},"PeriodicalIF":9.0,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/joim.20043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}