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1.
Age Ageing ; 53(2)2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38411410

RESUMEN

BACKGROUND: Understanding how analgesics are used in different countries can inform initiatives to improve the pharmacological management of pain in nursing homes. AIMS: To compare patterns of analgesic use among Australian and Japanese nursing home residents; and explore Australian and Japanese healthcare professionals' perspectives on analgesic use. METHODS: Part one involved a cross-sectional comparison among residents from 12 nursing homes in South Australia (N = 550) in 2019 and four nursing homes in Tokyo (N = 333) in 2020. Part two involved three focus groups with Australian and Japanese healthcare professionals (N = 16) in 2023. Qualitative data were deductively content analysed using the World Health Organization six-step Guide to Good Prescribing. RESULTS: Australian and Japanese residents were similar in age (median: 89 vs 87) and sex (female: 73% vs 73%). Overall, 74% of Australian and 11% of Japanese residents used regular oral acetaminophen, non-steroidal anti-inflammatory drugs or opioids. Australian and Japanese healthcare professionals described individualising pain management and the first-line use of acetaminophen. Australian participants described their therapeutic goal was to alleviate pain and reported analgesics were often prescribed on a regular basis. Japanese participants described their therapeutic goal was to minimise impacts of pain on daily activities and reported analgesics were often prescribed for short-term durations, corresponding to episodes of pain. Japanese participants described regulations that limit opioid use for non-cancer pain in nursing homes. CONCLUSION: Analgesic use is more prevalent in Australian than Japanese nursing homes. Differences in therapeutic goals, culture, analgesic regulations and treatment durations may contribute to this apparent difference.


Asunto(s)
Acetaminofén , Dolor , Femenino , Humanos , Australia , Acetaminofén/uso terapéutico , Estudios Transversales , Japón/epidemiología , Dolor/diagnóstico , Dolor/tratamiento farmacológico , Analgésicos Opioides/uso terapéutico , Casas de Salud
2.
J Gen Intern Med ; 38(16): 3517-3525, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37620717

RESUMEN

BACKGROUND: With rising worldwide population aging, the number of homebound individuals with multimorbidity is increasing. Improvement in the quality of home medical care (HMC), including medications, contributes to meeting older adults' preference for "aging in place" and securing healthcare resources. OBJECTIVE: To evaluate the changes in drug prescriptions, particularly potentially inappropriate medications (PIMs), among older adults receiving HMC in recent years, during which measures addressing inappropriate polypharmacy were implemented, including the introduction of clinical practice guidelines and medical fees for deprescribing. DESIGN: A cross-sectional study. PARTICIPANTS: Using data from the national claims database in Japan, this study included older adults aged ≥ 75 years who received HMC in October 2015 (N = 499,850) and October 2019 (N = 657,051). MAIN MEASURES: Number of drugs, prevalence of polypharmacy (≥ 5 regular drugs), major drug categories/classes, and PIMs according to Japanese guidelines were analyzed. Random effects logistic regression models were used to evaluate the differences in medications between 2015 and 2019, considering the correlation within individuals who contributed to the analysis in both years. KEY RESULTS: The number of drugs remained unchanged from 2015 to 2019 (median: 6; interquartile range: 4, 9). The prevalence of polypharmacy also remained unchanged at 70.0% in both years (P = 0.93). However, the prescription of some drugs (e.g., direct oral anticoagulants, new types of hypnotics, acetaminophen, proton pump inhibitors, and ß-blockers) increased, whereas others (e.g., warfarin, vasodilators, H2 blockers, acetylcholinesterase inhibitors, and benzodiazepines) decreased. Among the frequently prescribed PIMs, benzodiazepines/Z-drugs (25.6% in 2015 to 21.1% in 2019; adjusted odds ratio: 0.52) and H2 blockers (11.2 to 7.3%; 0.45) decreased, whereas diuretics (23.8 to 23.6%; 0.90) and antipsychotics (9.7 to 10.5%; 1.11) remained unchanged. CONCLUSIONS: We observed some favorable changes but identified some continuous and new challenges. This study suggests that continued attention to medication optimization is required to achieve safe and effective HMC.


Asunto(s)
Prescripción Inadecuada , Lista de Medicamentos Potencialmente Inapropiados , Humanos , Anciano , Prescripción Inadecuada/prevención & control , Japón/epidemiología , Polifarmacia , Estudios Transversales , Acetilcolinesterasa , Prescripciones de Medicamentos , Benzodiazepinas
3.
Geriatr Gerontol Int ; 24(4): 404-409, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38497333

RESUMEN

AIM: The purpose of the present study was to clarify the association of pneumonia admission with polypharmacy and specific drug use in community-dwelling older people. METHODS: Using health insurance and long-term care insurance data from Kure city in Japan, we retrospectively collected data for older community-dwelling people (aged ≥65 years) from April 2017 to March 2019. The outcome was pneumonia admission. We carried out multivariate logistic regression analysis to identify the association of pneumonia admission with polypharmacy (≥5 drugs), the use of psychotropic drugs or anticholinergics with adjustment for patient backgrounds, such as comorbidity, and the daily life independence level for the older people with disability. RESULTS: Of 59 040 older people, 4017 (6.8%) participants were admitted for pneumonia in 2 years. The ratio of polypharmacy, and the use of psychotropic drugs and anticholinergics in the admission group were significantly higher than the non-admission group. Multivariate logistic regression analysis showed that polypharmacy (odds ratio 1.29, 95% confidence interval 1.18-1.41), and the use of conventional antipsychotic drugs (odds ratio 1.39, 95% confidence interval 1.02-1.90), atypical antipsychotic drugs (odds ratio 1.67, 95% confidence interval 1.37-2.05) and anticholinergics (odds ratio 1.22, 95% confidence interval 1.13-1.33) were significantly associated with pneumonia admission. CONCLUSION: The present results suggest that polypharmacy, and the use of psychotropic drugs and anticholinergics are risk factors for pneumonia admission. Geriatr Gerontol Int 2024; 24: 404-409.


Asunto(s)
Antipsicóticos , Vida Independiente , Humanos , Anciano , Estudios Retrospectivos , Antipsicóticos/efectos adversos , Polifarmacia , Psicotrópicos/efectos adversos , Antagonistas Colinérgicos/efectos adversos
4.
Arch Gerontol Geriatr ; 106: 104873, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36446253

RESUMEN

AIMS: To investigate the influence of disability severity level on polypharmacy and the prescription of potentially inappropriate medication (PIM) using health insurance and long-term care (LTC) insurance claim data. METHODS: Data were obtained from a health-care insurance and long-term care insurance claims database of citizens of Kure city, Japan, in April 2017. Data including age, sex, and drug profile were obtained, and the level of LTC needs was used to measure disability level. Factors associated with polypharmacy (≥5 prescribed drugs) and PIM prescription (≥1 PIM) defined by STOPP-J were analyzed statistically. RESULTS: Among 67,169 people aged ≥65 (mean age 77.2 ± 7.9, male 40.7%), the frequency of polypharmacy increased with age until 85-89 (male 58.3%, female 57.6%) in both genders, and polypharmacy was most prevalent in those at the mildest LTC level (support level: male 68.9%, female 73.7%). PIM prescriptions was also frequent in those with LTC needs. On multiple logistic regression analysis, polypharmacy was significantly associated with older age and LTC needs, and PIM prescription was associated with older age and higher LTC level, suggesting that there is a large difference in prescription according to the person's age and disability level. CONCLUSION: Polypharmacy was prevalent especially in older persons which peaked at the age of 85-89 or at mild disability level, and PIM prescription was prevalent in those with older age and higher care levels. When optimizing polypharmacy or PIM prescription in older patients, healthcare providers should focus on not only age but also disability level.


Asunto(s)
Personas con Discapacidad , Lista de Medicamentos Potencialmente Inapropiados , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Prescripción Inadecuada , Vida Independiente , Polifarmacia , Factores de Riesgo
5.
Medicine (Baltimore) ; 102(21): e33552, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37233437

RESUMEN

Older adults often receive polypharmacy, including some medications for chronic diseases. Nutritional management after admission to a nursing home may enable to deprescribe some chronic disease medications. This study aimed to investigate the status of deprescribing of chronic disease medications among nursing home residents, and to assess the appropriateness based on changes of laboratory test values and nutritional status. A multi-center prospective cohort study was conducted in 6 Geriatric Health Services Facilities, a major type of nursing homes in Japan. Newly admitted residents aged ≥ 65 years who took ≥1 medication for hypertension, diabetes, or dyslipidemia at admission were recruited. Participants who stayed for 3 months were included in the analysis. Medications at admission and 3 months after admission and situations for deprescribing were investigated. Changes in body mass index, blood pressure, laboratory tests (e.g., cholesterol and hemoglobin A1c levels), energy intake, and International Classification of Functioning, Disability and Health staging were evaluated. Sixty-nine participants (68% female, 62% aged ≥ 85 years) were included. At admission, 60 participants had medications for hypertension, 29 for dyslipidemia, and 13 for diabetes. Those receiving lipid-modifying drugs (mainly statins) decreased from 29 to 21 (72%; P = .008), since their cholesterol levels was within the normal range or was low at admission, and they had no history of cardiovascular events. However, there were no statistically significant changes in the frequencies of antihypertensive drugs (60 to 55; 92%; P = .063) or antidiabetic drugs (13 to 12; 92%; P = 1.000). During the 3-month observation, body mass index and diastolic blood pressure decreased, while energy intake and serum albumin level increased. Nutritional management after admission to a ROKEN may facilitate appropriate deprescribing of lipid-modifying drugs, by offseting the effects of discontinuation of these drugs.


Asunto(s)
Servicios de Salud para Ancianos , Hipertensión , Anciano , Humanos , Femenino , Masculino , Estudios Prospectivos , Casas de Salud , Hipertensión/tratamiento farmacológico , Lípidos , Polifarmacia
6.
Gan To Kagaku Ryoho ; 39 Suppl 1: 3-5, 2012 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-23268883

RESUMEN

Quantitative and qualitative analyses of a caring family are needed to improve home care. We propose a three-dimensional quantitative evaluation of family functioning. The first dimension is food, clothing, and shelter; the second dimension is patient, medical, and caring conditions; and the third dimension is the caring family condition. We used the home care score and Family Adaptability and Cohesion Evaluation Scale at Kwansei Gakuin(FACESKG)IV for the quantitative evaluation of family functioning. Narrative medicine and ethnography are valuable for the qualitative evaluation of a caring family.


Asunto(s)
Cuidadores , Servicios de Atención de Salud a Domicilio , Vestuario , Familia , Alimentos , Tareas del Hogar
7.
Geriatr Gerontol Int ; 22(8): 648-652, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35790216

RESUMEN

AIM: Previous studies have shown temporal trends in the number of gastrostomies until 2016, but the recent trend is yet to be analyzed. This study aimed to evaluate temporal trends in gastrostomy (mostly percutaneous endoscopic gastrostomy) in older adults in Japan in more recent years. METHODS: We extracted data on the numbers of gastrostomies and swallowing function assessment prior to gastrostomy, using the national aggregated open data (NDB Open Data) from 2014 to 2019. RESULTS: Adults in their 80s accounted for the largest portion of gastrostomy during the study period. A decreasing trend in the total number of gastrostomy was observed in older adults from 2014 to 2016, but became almost stable thereafter (57 103 in 2014, 47 228 in 2016, and 47 944 in 2019). The age group-stratified numbers of gastrostomy per 100 000 individuals decreased by -33.9% (≥90 years group) to -6.1% (65-69 years group) from 2014 to 2019. The implementation rate of the swallowing function assessment remained relatively low, despite a slight increase (21.4% in 2015 to 23.7% in 2019). CONCLUSION: We showed that the total number of gastrostomies remained almost stable after 2016 despite population aging. We considered that the avoidance of gastrostomy in frail or disabled older adults might explain the decrease, particularly for those aged over 80 years. Our findings would regain attention to appropriate decision-making for gastrostomy. Geriatr Gerontol Int 2022; 22: 648-652.


Asunto(s)
Nutrición Enteral , Gastrostomía , Anciano , Anciano de 80 o más Años , Humanos , Japón/epidemiología
8.
Artículo en Inglés | MEDLINE | ID: mdl-35831182

RESUMEN

OBJECTIVES: This study aimed to evaluate the prescription patterns of drugs during the last year of life in homebound older adults who received home medical care. METHODS: We used a nationwide claims database in Japan and selected older adults aged ≥75 years who received home medical care services from ≥12 months before their death. We evaluated medications prescribed 12 months before death (month 12), 3 months before death (month 3) and in the last month of life (month 1). We explored the factors associated with the decreased number of cardiovascular preventive drugs from month 12 to both month 3 and month 1. RESULTS: A total of 118 661 participants were included, and the majority were aged ≥90 years and women. The prevalence of cardiovascular preventive drugs decreased but remained common in month 1, which included antihypertensives (34.7%), antiplatelets (15.9%), oral anticoagulants (7.6%), antidiabetic drugs (7.3%) and lipid-lowering drugs (6.1%). The relative decrease from month 12 to month 1 was the largest for lipid-lowering drugs (44.8%) and the smallest for oral anticoagulants (13.6%). Among other drugs, laxatives (enema), antiemetics, oral corticosteroids, analgesics, expectorants, bronchodilators and antibiotics showed a large relative increase. Older age, duration of home medical care services for <1 year and diagnoses of cancer, dementia and Parkinson's disease were associated with a greater likelihood of a decreased number of cardiovascular preventive drugs. CONCLUSIONS: There is room for deprescribing to avoid inappropriate polypharmacy by balancing preventive and symptom management drugs in those receiving home medical care with a limited life expectancy.

9.
Medicine (Baltimore) ; 101(6): e27451, 2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35147084

RESUMEN

BACKGROUND: The importance of fall prevention rehabilitations has been well recognized. Recently telerehabilitation was developed, however, there have been no reports on telerehabilitation with direct support from specialists for fall prevention among the elderly. We herein reported telerehabilitation by caregivers educated by our novel educational program. METHODS: Caregivers were educated with our educational program using a telelecture system and supported telerehabilitation following instructions from rehabilitation specialists in our university using the telemedicine system every two to four weeks for three months. Caregivers were assessed with our original questionnaire before and after the telelecture. Participants were assessed by the Berg Balance Scale (BBS), Timed Up & Go test (TUG test), Hand-held dynamometer (HHD) and Mini-Mental State Examination (MMSE) before and after telerehabilitation. Wilcoxon's signed-rank test was used for the statistical analyses. A value of P<.05 was considered statistically significant. RESULTS: Nine elderly people were enrolled. The mean age was 84.7 (78-90) years old and the sex ratio was 1:8 (males:females). The average number of telerehabilitation sessions was 4.7. The average score of nineteen caregivers before the lecture was 15.3, while that after the lecture was 18.3. Caregivers' understanding was significantly increased after the telelecture (P<.001). No adverse events occurred during the study period. The median values of the BBSs, TUG test, right and left HHD and MMSE before and after 3 months' telerehabilitation were 43 (95% confidence interval [CI]: 40.10, 49.01) and 49 (95% CI: 41.75, 50.91), 17.89 (95% CI: 15.51, 23.66) and 18.53 (95% CI: 14.56, 25.67), 7.95 (95% CI: 4.38, 10.14) and 11.55 (95% CI: 7.06, 13.55), 9.85 (95% CI: 6.79, 12.59) and 13.20 (95% CI: 7.96, 14.42), and 19 (95% CI: 12.34, 21.66) and 16 (95% CI: 10.81, 21.00), respectively. Although approximately half of the participants showed improvement in the BBS, TUG test, right and left HHD and MMSE, no significant changes were observed (P=.7239, P=.3446, P=.1023, P=.3538 and P=.8253, respectively). CONCLUSIONS: Our telerehabilitation program exhibited significant effects in elderly people and improved the degree of understanding concerning rehabilitation among caregivers in facilities for elderly people.


Asunto(s)
Accidentes por Caídas/prevención & control , Cuidadores/educación , Telemedicina , Telerrehabilitación , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Fuerza Muscular
10.
BMJ Open ; 11(4): e045787, 2021 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-34468334

RESUMEN

OBJECTIVES: To evaluate the prescription and discontinuation of psychotropic drugs (PD) and drugs with anticholinergic properties (DAP) in residents with dementia admitted to Roken, a major type of long-term care facility in Japan. DESIGN: Cohort study. SETTING: A nationwide questionnaire survey across 3598 Roken in Japan in 2015 (up to five randomly selected residents per facility). PARTICIPANTS: This study included 1201 residents from 343 Roken (response rate: 10%). We determined the presence and severity of dementia using a nationally standardised measure. PRIMARY AND SECONDARY OUTCOME MEASURES: Prescriptions of PD and DAP at admission and 2 months after admission were evaluated. Multivariable logistic regression was used to evaluate the associations of residents' baseline characteristics with prescriptions or discontinuation. RESULTS: Prescription rates decreased for antidementia drugs (19.4% to 13.0%), hypnotics (25.1% to 22.6%) and anxiolytics (12.3% to 10.7%), whereas those for other PD, such as antipsychotics (13.2% to 13.6%), antidepressants (7.4% to 6.7%), antiepileptic drugs (7.1% to 7.8%) and DAP (35.2% to 36.6%) did not statistically significantly decrease. Some factors were associated with the prescriptions, for example, for antipsychotics, older age (≥85 years) (adjusted OR (aOR), 0.60; 95% CI 0.43 to 0.85) and being bedridden (aOR 0.67; 95% CI 0.47 to 0.97) were associated with a lower use of antipsychotics, whereas severe dementia was associated with a higher use of antipsychotics (aOR 3.26; 95% CI 2.26 to 4.70). At an individual level, a quarter of residents prescribed PD or DAP at admission had discontinued at least one PD or DAP, respectively, 2 months after admission. Antidementia drug use in severe dementia (aOR 1.86; 95% CI 1.04 to 3.31) and PD use in older age (aOR 1.61; 95% CI 1.00 to 2.60; in residents with disabling dementia) were associated with discontinuation. CONCLUSIONS: There is possible scope for deprescribing PD and DAP in Roken residents with dementia to mitigate the risks of adverse events.


Asunto(s)
Demencia , Instituciones de Cuidados Intermedios , Preparaciones Farmacéuticas , Anciano , Antagonistas Colinérgicos/uso terapéutico , Estudios de Cohortes , Demencia/tratamiento farmacológico , Humanos , Japón , Psicotrópicos/uso terapéutico
11.
Geriatr Gerontol Int ; 20(10): 961-966, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32812703

RESUMEN

AIM: Studies of medication use in patients with a percutaneous endoscopic gastrostomy (PEG) tube have not been conducted adequately. The aim of this study was to describe medication use of care-dependent older adults with PEG and evaluate whether potential prescribing omissions (PPO) would affect the cause of death or acute illness. METHODS: In a geriatric long-term care hospital, 116 inpatients aged ≥65 years with insertion of a PEG tube because of dysphagia were enrolled and followed for 2 years: 2016-2018. The patients were divided into two groups, i.e., group A (who died between 2016 and 2018) and group B (who continued to be hospitalized in 2018). Clinical data and prescribed medications were recorded. Logistic regression models were conducted to assess the associations between survival and variables: age, gender, serum albumin level, serum creatinine level, body mass index (BMI), number of drugs and PPO. RESULTS: The patients' mean age was 85.3 ± 10.2 years, 57.8% were women and the mean number of drugs was 6.8 ± 3.5. Medications for managing symptoms, such as constipation and gastrointestinal symptoms, were commonly prescribed. The most common PPO medications were antiplatelet agents and anticoagulants. On logistic regression analysis, PPO had no influence on the cause of death or acute illness. Lower age, higher serum albumin level and body mass index were associated with survival in both univariate and multivariate models. CONCLUSIONS: Polypharmacy was prevalent in patients with PEG. Given the finding that PPO had no influence on health outcome, rational deprescribing could be warranted. Geriatr Gerontol Int 2020; 20: 961-966.


Asunto(s)
Causas de Muerte , Deprescripciones , Prescripciones de Medicamentos/estadística & datos numéricos , Gastrostomía , Intubación Gastrointestinal , Anciano , Anciano de 80 o más Años , Nutrición Enteral , Femenino , Humanos , Japón , Cuidados a Largo Plazo , Masculino , Polifarmacia , Estudios Retrospectivos
12.
Arch Gerontol Geriatr ; 88: 104016, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32045709

RESUMEN

OBJECTIVES: No established approaches exist for the pharmacological management of cardiovascular diseases (CVDs) in residents of long-term care facilities (LTCFs). This study aimed to evaluate the use of drugs for CVD prevention and treatment (CVD-related drugs) in a major type of LTCF in Japan. METHODS: This study included 1318 randomly selected residents at 349 intermediate care facilities for older adults (called Roken). Prescriptions were investigated at admission and two months after admission according to therapeutic categories. Logistic regression was used to identify residents' characteristics that were associated with prescriptions of CVD-related drugs. RESULTS: Prescriptions of all types of drugs and CVD-related drugs decreased in 36 % and 16 % of residents, respectively. Half of the residents received antihypertensives, a quarter received antiplatelets and diuretics, whereas one-tenth received antidiabetics, oral anticoagulants, and lipid-modifying drugs. The prevalence of most of individual drug categories were similar among residents with different physical or cognitive function, except for fewer antihypertensive and lipid-modifying drugs in those with severe cognitive disability. Adjusted analyses for prescriptions at two months after admission revealed that bedridden residents were more likely to be prescribed diuretics but less likely to be prescribed antihypertensives, antiplatelets, or lipid-modifying drugs. Residents with severe cognitive disability were less likely to be prescribed antihypertensives or lipid-modifying drugs. A known history of cardiovascular events was associated with greater use of CVD-related drugs. CONCLUSION: CVD-related drugs were commonly prescribed for Roken residents, including those with low physical and cognitive functions. Deprescribing may contribute to the optimization of pharmacotherapy in LTCF residents.


Asunto(s)
Antihipertensivos , Enfermedades Cardiovasculares , Instituciones de Cuidados Intermedios , Inhibidores de Agregación Plaquetaria , Anciano , Antihipertensivos/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Humanos , Hipolipemiantes/uso terapéutico , Japón/epidemiología , Cuidados a Largo Plazo , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pautas de la Práctica en Medicina , Instituciones de Cuidados Especializados de Enfermería
13.
Ann Geriatr Med Res ; 23(1): 27-30, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32743282

RESUMEN

BACKGROUND: Although the notion of percutaneous endoscopic gastrostomy (PEG) tube placement for patients with dementia has been changing, the number of cases of PEG placement remains high as Japan has become a super-aged society. However, there is insufficient research about the clinical course of dementia patients with PEG, especially regarding PEG extubation after regaining full oral intake. This case series aimed to reveal the demographic data of patients who successfully underwent PEG extubation and to identify clinical factors that might help predict eventual resumption. METHODS: This retrospective case series was identified in a private, community-based long-term care hospital in Sapporo, Japan. Inclusion criteria for the series were: 1) age, ≥75 years, 2) diagnosis of any type of dementia, and 3) resumption of full oral intake after removal of PEG tubes. RESULTS: Eight female patients were identified. Decreased oral intake was triggered by acute medical conditions, such as infectious enteritis. A trial of oral intake was initiated mostly by speech therapists. A majority of the patients ate pureed food. The patients aged ≥85 years with advanced dementia could be weaned from PEG tubes. CONCLUSION: The series indicates that even patients with limited life expectancy could recover swallowing function by receiving appropriate guidance and care. Constant evaluation for swallowing function even after PEG insertion may be important for PEG extubation.

15.
J Clin Invest ; 126(4): 1367-82, 2016 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-26974156

RESUMEN

Most skin cancers develop as the result of UV light-induced DNA damage; however, a substantial number of cases appear to occur independently of UV damage. A causal link between UV-independent skin cancers and chronic inflammation has been suspected, although the precise mechanism underlying this association is unclear. Here, we have proposed that activation-induced cytidine deaminase (AID, encoded by AICDA) links chronic inflammation and skin cancer. We demonstrated that Tg mice expressing AID in the skin spontaneously developed skin squamous cell carcinoma with Hras and Trp53 mutations. Furthermore, genetic deletion of Aicda reduced tumor incidence in a murine model of chemical-induced skin carcinogenesis. AID was expressed in human primary keratinocytes in an inflammatory stimulus-dependent manner and was detectable in human skin cancers. Together, the results of this study indicate that inflammation-induced AID expression promotes skin cancer development independently of UV damage and suggest AID as a potential target for skin cancer therapeutics.


Asunto(s)
Carcinoma de Células Escamosas/enzimología , Citidina Desaminasa/metabolismo , Neoplasias Experimentales/enzimología , Neoplasias Cutáneas/enzimología , Piel/enzimología , Rayos Ultravioleta/efectos adversos , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Citidina Desaminasa/genética , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ratones Desnudos , Mutación , Neoplasias Experimentales/genética , Neoplasias Experimentales/patología , Especificidad de Órganos , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Piel/patología , Neoplasias Cutáneas/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
16.
J Dermatol ; 43(5): 547-52, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26508292

RESUMEN

Preceding this study, we observed two cases of concurrent postoperative gluteal skin and muscle damage with extremely high serum creatine kinase (CK) levels, both of which were unrelated to pressure-induced tissue injury. However, postoperative gluteal skin damage accompanied by gluteal muscle damage has not been previously reported and the association between gluteal skin damage, gluteal muscle damage and pressure-induced tissue injury has not previously been investigated. Therefore, we conducted this study to determine the postoperative incidence of gluteal skin damage associated with gluteal muscle damage and assess associations with postoperative serum CK levels and pressure-induced tissue injury. We prospectively evaluated postoperative incidence of gluteal skin damage and measured serum CK levels in 929 consecutive patients who underwent abdominal, urological or gynecological surgery at our hospital. Magnetic resonance imaging (MRI) of the pelvis was performed in 67 patients who consented. As a result, two of 929 patients developed postoperative gluteal skin damage accompanied by gluteal muscle damage. Gluteal muscle damage without gluteal skin damage was observed in 23 of the 67 patients who underwent MRI, and volumes of damaged gluteal muscle and postoperative serum CK levels were positively correlated. Both gluteal skin and muscle damage were distinguishable from pressure-induced tissue injury. Based on the results of this study, we could confirm the occurrence of postoperative gluteal skin damage, distinct from pressure sores, accompanied by gluteal muscle damage. We also revealed latent development of postoperative gluteal muscle damage, distinguishable from compression-induced tissue injury, without accompanying gluteal skin damage.


Asunto(s)
Creatina Quinasa/sangre , Músculo Esquelético/lesiones , Complicaciones Posoperatorias/epidemiología , Piel/lesiones , Anciano , Anciano de 80 o más Años , Nalgas , Femenino , Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Humanos , Incidencia , Japón/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pelvis/diagnóstico por imagen , Complicaciones Posoperatorias/sangre , Úlcera por Presión/sangre , Úlcera por Presión/epidemiología , Estudios Prospectivos , Procedimientos Quirúrgicos Urológicos/efectos adversos
18.
Antioxid Redox Signal ; 6(3): 561-70, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15130282

RESUMEN

Reactive oxygen species (ROS) are associated not only with initiation, but also with promotion and progression in the multistage carcinogenesis model. In the present review, we will focus on the involvement of ROS in skin carcinogenesis, especially that induced by ultraviolet (UV) radiation. UV-specific DNA damage has been well studied thus far. However, recent reports have revealed the previously unknown participation of oxidative stress in UV-induced skin carcinogenesis. Indeed, in addition to transition-type mutations at dipyrimidine sites, G:C to T:A transversions, which may be induced by the presence of 8-oxoguanine during DNA replication, are frequently observed in the ras oncogene and p53 tumor suppressor gene in human skin cancers of sun-exposed areas and in UV-induced mouse skin cancers. Recent studies have shown that not only UV-B, but also UV-A is involved in UV-induced carcinogenesis. A wide variety of biological phenomena other than direct influence by UV, such as inflammatory and immunological responses and oxidative modifications of DNA and proteins, appear to play roles in UV-induced skin carcinogenesis. Furthermore, it has become clear that genetic diseases such as xeroderma pigmentosum show deficient repair of oxidatively modified DNA lesions. The involvement of ROS in skin carcinogeneisis caused by arsenic and chemical carcinogens will also be discussed.


Asunto(s)
Guanina/análogos & derivados , Neoplasias Inducidas por Radiación/patología , Especies Reactivas de Oxígeno , Neoplasias Cutáneas/patología , Animales , ADN/genética , Daño del ADN , Genes p53 , Guanina/química , Humanos , Ratones , Modelos Biológicos , Mutación , Rayos Ultravioleta
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