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1.

Background

Low-dose rate brachytherapy is a well established treatment modality of oral cancer. Data about high-dose rate (HDR) brachytherapy are still sparse with various fractionation schedules and heterogeneous results.

Aim

The aim of our retrospective study was to evaluate the results of HDR brachytherapy with doses of 3 Gy twice daily.

Patients and methods

Twenty patients with squamous cell tongue cancer were treated in the years 2001–2009 by exclusive HDR BT 18 × 3 Gy twice daily. The plastic tube technique was used. Median follow up was 47 months (7.8–118) since brachytherapy.

Results

The local and locoregional control was 85% and 68%, respectively. Bone necrosis developed in one case treated without mandibular shielding and soft tissue necrosis in 2 cases.

Conclusion

It can be concluded that HDR brachytherapy with 18 × 3 Gy twice daily is safe with promising local control. The risk of nodal recurrences is substantial.  相似文献   

2.

Objective

To compare the efficacy and safety of high dose rate (HDR) and low dose rate (LDR) brachytherapy in treating early-stage oral cancer.

Data Sources

A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies.

Study Selection

Only randomized controlled trials (RCT) and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III) were of interest.

Data Extraction and Synthesis

Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR) met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62–2.01), overall mortality (OR = 1.01, CI 95% 0.61–1.66) and Grade 3/4 complications (OR = 0.86, CI 95% 0.52–1.42).

Conclusions

This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.  相似文献   

3.

Aim

This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer.

Background

Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known.

Materials and methods

Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4–81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6–79.2 Gy), respectively.

Results

The time between the last session and the last treatment follow up was a median of 10 months (range, 3–24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones.

Conclusions

RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome.  相似文献   

4.

Aim

To report outcomes for patients with para-aortic lymph node positive cervical cancer treated with a dynamic field-matching technique.

Background

PET staging of cervical cancer has increased identification of patients with para-aortic lymph node metastasis. IMRT enables dose escalation in this area, but matching IMRT fields with traditional whole pelvis fields presents a challenge.

Materials and methods

From 2003 to 2012, 20 patients with cervical cancer and para-aortic lymph node metastasis were treated utilizing the dynamic field-matching technique. As opposed to single-isocenter half-beam junction techniques, this technique employs wedge-shaped dose junctions for the abutment of fields. We reviewed the records of all patients who completed treatment with the technique and abstracted treatment, toxicity, and disease-related outcome data for analysis.

Results

Median prescribed dose to the whole pelvis field was 45 Gy and para-aortic IMRT field 50.4 Gy. All but 3 patients underwent HDR (13 pts) or LDR (4 pts) brachytherapy. All patients developed lower GI toxicity; 10 grade 1, 9 grade 2, and 1 grade 4 (enterovaginal fistula). Median DFS was 12.4 months with 1 and 2-year DFS 60.0% and 38.1%. One-year OS was 83.7% and 2-year OS, 64.4%. A total of 10 patients developed recurrence; none occurred at the matched junction.

Conclusions

The dynamic field-matching technique provides a means for joining conventional whole pelvis fields and para-aortic IMRT fields that substantially reduces dose deviations at the junction due to field mismatch. Treatment with the dynamic matching technique is simple, effective, and tolerated with no apparent increase in toxicity.  相似文献   

5.

Aim/background

We sought to determine the tolerance level and complication rates of the vaginal vault to combined high-dose-rate intra-cavitary brachytherapy with concomitant chemo-radiotherapy.

Patients and methods

A retrospective review of medical records of all the patients who received definitive chemo-radiotherapy for cervical cancer between 1998 and 2002 was undertaken. The records were reviewed for doses and for radiation-associated early and late sequelae of the vagina, rectum and bladder. Cumulative biological effective dose was calculated for two reference vaginal surface points.

Results

Fifty patients were included. Average age at diagnosis was 54 years. Median follow-up was 59 months. There were no recorded instances of acute grade IV toxicity. Maximal high-dose-rate vaginal surface dose (upper central point) was 103 Gy, and maximal brachytherapy lateral surface dose was 70 Gy. Maximal cumulative biological effective dose for the lateral surface reference point was 465.5 Gy3, and the maximal cumulative biological effective dose for the superior reference point was 878.6 Gy3. There were no cases of vaginal necrosis or fistulas, and no cases of grade IV late vaginal, rectal or bladder toxicity. No correlation was found between the maximal vaginal surface dose and vaginal, rectal or bladder toxicity.

Conclusions

The maximal surface HDR brachytherapy dose of 103 Gy and the maximal cBED of 878.6 Gy3 were not associated with fistula or necrosis or other grade 3–4 vaginal complications. Concomitant chemo-radiotherapy, including pelvic radiotherapy and high-dose-rate intracavitary brachytherapy, is relatively safe for cervical cancer patients.  相似文献   

6.

Purpose

Standard treatment for early-stage endometrial cancer involves surgery (when possible) followed by brachytherapy or external-beam radiotherapy (EBRT) for high-risk tumors. EBRT is not without toxicity, meaning that it could be difficult to complete for elderly patients, who typically have decreased reserve and resistance to stressors.

Patients and methods

Patients aged 70 and over treated between April 2009 and May 2013 for endometrial cancer and received IMRT (Intensity-Modulated Radiation Therapy) were included in this observational study. IMRT could be performed as adjuvant treatment or as an exclusive treatment for patients not amenable to surgery. The primary endpoints of this study were to assess the feasibility and toxicity of pelvic IMRT in this population. Secondary endpoints were to assess disease-specific survival, overall survival, and local control. Predictors of toxicity were also explored.

Results

Forty seven consecutive patients were included in the analysis. Median age at diagnosis was 75 years (range, 70–89 years). Eleven patients were aged 80 years and older. Toxicities were found in thirty four patients (72%) during treatment. Among these, toxicity did not exceed grade 2 for 32 patients (68%). Two patients had a grade 3 toxicity (4%). Overall survival rates were 87% and 83% at 1 and 2 years, respectively. Six patients (12.8%) had a local relapse and nine others (19.1%) had distant relapse.

Conclusions

Pelvic helical IMRT for patients aged 70 and older is feasible with full standard radiation doses, showing that age greater than 70 should not be considered as a reason not to perform optimal treatment.  相似文献   

7.

Background

The use of HDR in the treatment of soft tissue sarcoma had been on the rise. However, there was limited study to evaluate the effect of different fractionation schemes on soft tissue and the optimal HDR scheme.

Aims

We aimed to assess the histopathologic changes on soft tissue after different HDR brachytherapy doses.

Methods

The subjects were divided into three groups. Each group included 10 limbs. Group A had only an applicator without radiation, group B received a total of 24 Gy at 6 Gy per fraction, twice a day, and group C received a total of 13.5 Gy in a single fraction. The histopathologic findings were grouped into soft tissue pathology-1 (edema, inflammation, endothelial proliferation, necrosis) and soft tissue pathology-2 (atrophy, calcification, vascular hyalinization, fibrosis) (STP-1–2).

Results

The highest mean grade values of STP-1 and STP-2 were observed in group C (0.95 and 1.45) in comparison to group A (0.45 and 0.85) and group B (0.65 and 0.9). The difference in STP-1 was found significant only between groups A and C and the difference in STP-2 was found both between groups A and C and groups B and C.

Conclusion

In our experimental study it was shown that the fractionated interstitial HDR had both lower rate and severity of toxicity in comparison to a single high dose fraction. Before using a single fractionated regimen in the clinic, the increased morbidity related to the irreversible early toxicities or progressive late toxicities should be kept in mind.  相似文献   

8.

Background

Limited data exist regarding toxicity and quality of life (QOL) after post-prostatectomy intensity modulated radiation therapy (IMRT) and whether pelvic nodal RT influences these outcomes.

Methods

118 men were treated with curative-intent RT after radical prostatectomy. 69 men (58%) received pelvic nodal RT. QOL data and physician-assigned toxicity were prospectively collected. Changes in QOL from baseline were assessed with Wilcoxon signed-rank tests and risk factors associated with each domain were identified with generalized estimating equation (GEE) models. Late freedom from (FF) toxicity was estimated by the Kaplan-Meier method and comparisons were tested using the log-rank test.

Results

Urinary irritation/obstruction, bowel, and sexual domain scores declined at 2 months (all P ≤ 0.01) but were no different than baseline at subsequent visits through 4 years of follow-up. At 4 years, FF grade 2+ GI toxicity was 90% and FF grade 2+ GU toxicity was 89%. On GEE analysis, pelvic nodal RT was associated with decreased bowel function (P = 0.09) and sexual function (P = 0.01). On multivariate analysis, however, there was no significant association with either decreased bowel (P = 0.31) or sexual (P = 0.84) function. There was also no association with either FF grade 2+ GI toxicity (P = 0.24) or grade 2+ GU toxicity (P = 0.51).

Conclusions

Receipt of pelvic nodal RT was not associated with inferior QOL or toxicity compared to prostate bed alone RT. For the entire cohort, RT was associated with only temporary declines in patient-reported urinary, bowel, or sexual QOL.  相似文献   

9.

Objective

To assess the safety of VivaGel® used vaginally twice daily for 14 days among healthy, sexually-abstinent women, aged 18–24 years in the USA and Kenya.

Design

Randomized placebo controlled trial.

Methods

Participants were randomized 2∶1, VivaGel to placebo. Safety was assessed by comparing genitourinary (GU) adverse events (AEs), colposcopy findings, vaginal lactobacilli and laboratory abnormalities by arm.

Results

Fifty-four women were enrolled; 35 in the VivaGel arm and 19 in the placebo arm. Twenty-six (74%) and 10 (53%) women reported taking all doses of VivaGel and placebo, respectively. No grade 3 or 4 AEs, or serious AEs occurred. Twenty-five (71%) participants in the VivaGel arm compared to 10 (53%) participants in the placebo arm had at least one grade 1 or 2 GU AE associated with product use (RR = 1.4, 95% CI 0.8-2.2). All seven grade 2 GU AEs associated with product use occurred among four women in the VivaGel arm. Vulvar and cervical erythema, cervical lesions, symptomatic BV, urinary frequency and metrorrhagia were more common in the VivaGel arm than the placebo arm. Twenty-nine (83%) participants in the VivaGel arm had a colposcopic finding compared to 10 (53%) participants in the placebo arm (RR = 1.6, 95%CI = 1.0-2.5). Two women in the VivaGel arm prematurely discontinued product use themselves due to a reported GU AE. Persistence of H2O2-producing and non-producing lactobacilli did not differ by study arm.

Conclusions

GU AEs and colposcopic findings consistent with mild epithelial irritation and inflammation occurred more commonly among women in the VivaGel arm.

Trial Registration

ClinicalTrials.gov NCT003311032  相似文献   

10.

Aim

To calibrate Ir-192 high dose rate (HDR) brachytherapy source using different calibration methods and to determine the accuracy and suitability of each method for routine calibrations.

Background

The source calibration is an essential part of the quality assurance programme for dosimetry of brachytherapy sources. The clinical use of brachytherapy source requires an independent measurement of the air kerma strength according to the recommendations of medical physics societies.

Materials and methods

The Ir-192 HDR brachytherapy source from Gammamed plus machine (Varian Medical Systems, Palo Alto, CA) was calibrated using three different procedures, one using the well-type ionization chamber, second by the in-air calibration method and third using solid water phantoms. The reference air kerma rate (RAKR) of the source was determined using Deutsche Gesellschaft fur Medizinische Physik (DGMP) recommendations.

Results

The RAKR determined using different calibration methods are in good agreement with the manufacturer stated value. The mean percentage variations of 0.21, −0.94, −0.62 and 0.58 in RAKR values with respect to the manufacturer quoted values were observed with the well-type chamber, in-air calibration, cylindrical phantom and slab phantom measurements, respectively.

Conclusion

Measurements with a well-type chamber are relatively simple to perform. For in-air measurements, the indigenously designed calibration jig provides an accurate positioning of the source and chamber with minimum scatter contribution. The slab phantom system has an advantage that no additional phantom and chamber are required other than those used for external beam therapy dosimetry. All the methods of calibration discussed in this study are effective to be used for routine calibration purposes.  相似文献   

11.

Background

In 2008, the United States Preventive Services Task Force recommended against prostate specific antigen (PSA) testing for cancer screening in men age 75+.

Purpose

To assess PSA screening by primary care physicians (PCPs) before and after recommendations.

Methods

In 2013, this retrospective cohort study analyzed PCPs in Texas with 20+ male patients aged 75+ in both 2007 and 2010, with Parts A and B Medicare. The main outcome was percent of PCP’s male patients 75+ who received PSA testing ordered by the PCP in 2007 and 2010, with no recent symptoms suggestive of prostate cancer.

Results

In both 2007 and 2010, 1,083 PCPs cared for at least 20 men aged 75 or older. The rate of PSA screening ordered by PCPs was 33.2% in 2007 and 30.6% in 2010. In multilevel analyses controlling for patient characteristics, the variation in PSA screening attributable to the PCP (intraclass correlation coefficient) increased from 23% in 2007 to 26% in 2010, p<0.001. Men with PCPs older than age 60 had 9% lower odds (95% CI, 1–17%) in 2010 compared to 2007 of receiving a PSA test, vs. a 4% increase (95% CI, 4% decrease to 12% increase) in men with PCPs aged 50 or younger. Patients with Board Certified PCPs had a 12% lower odds (95% CI, 8% to 16%) from 2007 to 2010, vs. 2% increase (95% CI 11% decrease to 18% increase) in men with PCPs without board certification.

Conclusions

The USPSTF recommendation did not increase consensus among PCPs regarding PSA screening of older men.  相似文献   

12.

Aim

The aim of this work was to assess the suitability of the use of a Gafchromic EBT2 film for the measurement of anisotropy function for microSelectron HDR 192Ir (classic) source with a comparative dosimetry method using a Gafchromic EBT2 film and thermoluminescence dosimeters (TLDs).

Background

Sealed linear radiation sources are commonly used for high dose rate (HDR) brachytherapy treatments. Due to self-absorption and oblique filtration of radiation in the source capsule material, an inherent anisotropy is present in the dose distribution around the source which can be described by a measurable two-dimensional anisotropy function, F(r, θ).

Materials and methods

Measurements were carried out in a specially designed and locally fabricated PMMA phantom with provisions to accommodate miniature LiF TLD rods and EBT2 film dosimeters at identical radial distances with respect to the 192Ir source.

Results

The data of anisotropy function generated by the use of the Gafchromic EBT2 film method are in agreement with their TLD measured values within 4%. The produced data are also consistent with their experimental and Monte Carlo calculated results for this source available in the literature.

Conclusion

Gafchromic EBT2 film was found to be a feasible dosimeter in determining anisotropy in the dose distribution of 192Ir source. It offers high resolution and is a viable alternative to TLD dosimetry at discrete points. The method described in this paper is useful for comparing the performances of detectors and can be applied for other brachytherapy sources as well.  相似文献   

13.

Aim

Report the outcome of 8 patients (pts) with breast cancer (BC) treated with Tamoxifen (TAM) that developed malignant mixed Müllerian tumor (MMMT) and rare uterine sarcoma (RUS).

Patients and methods

Retrospective study based on data collected from the department medical records between April 1999 and September 2010 among 583 pts with endometrial cancer, 36 pts with MMMT and RUS histopathology. Among them, 8 pts underwent TAM between 4 and 10 years due to a previous diagnosis of BC; all pts were post-menopausal with regular gynecological surveillance; 6 pts (75%) with abnormal uterine bleeding. The diagnosis of 6 pts (MMMT) and 2 pts (RUS) occurred at median interval of 8 years (range 4–12) after initial BC treatment. Pts underwent surgical treatment and were staged as stage I (3pts), IIIA (3pts) and IIIC (2 pts) (FIGO 1988); followed by whole pelvis irradiation (50 Gy) and intracavitary HDR brachytherapy boost (24 Gy). Two pts underwent chemotherapy (CT). Overall and disease free survival was calculated by Kaplan Meier method.

Results

With a median follow-up of 47 months (range 17–130), 3 pts remain alive recurrence-free of BC and RUS. Four pts died with distant metastasis within the first follow-up year, without BC. One pt died from non-related cancer cause. No evidence of local recurrence was found in the whole group of pts. At two years, DFS and OS were 40% and 80%, respectively.

Conclusion

As reported in the literature, TAM administration and causal effect on MMMT and RUS in BC pts is still unknown. No reports about outcome from these specific pts were found.  相似文献   

14.

Introduction

Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML.

Trial Design

Prospective, randomised, open, phase II trial with parallel group design and fixed sample size.

Patients and Methods

Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of <20,000/µl at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint.

Results

Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days.

Conclusions

The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm.

Trial Registration

This trial is registered at clinical trials.gov (identifier: NCT00915252).  相似文献   

15.
16.

Objectives

We examined the social distribution of a comprehensive range of cardiovascular risk factors (CVRF) in a Swiss population and assessed whether socioeconomic differences varied by age and gender.

Methods

Participants were 2960 men and 3343 women aged 35–75 years from a population-based survey conducted in Lausanne, Switzerland (CoLaus study). Educational level was the indicator of socioeconomic status used in this study. Analyses were stratified by gender and age group (35–54 years; 55–75 years).

Results

There were large educational differences in the prevalence of CVRF such as current smoking (Δ = absolute difference in prevalence between highest and lowest educational group:15.1%/12.6% in men/women aged 35–54 years), physical inactivity (Δ = 25.3%/22.7% in men/women aged 35–54 years), overweight and obesity (Δ = 14.6%/14.8% in men/women aged 55–75 years for obesity), hypertension (Δ = 16.7%/11.4% in men/women aged 55–75 years), dyslipidemia (Δ = 2.8%/6.2% in men/women aged 35–54 years for high LDL-cholesterol) and diabetes (Δ = 6.0%/2.6% in men/women aged 55–75 years). Educational inequalities in the distribution of CVRF were larger in women than in men for alcohol consumption, obesity, hypertension and dyslipidemia (p<0.05). Relative educational inequalities in CVRF tended to be greater among the younger (35–54 years) than among the older age group (55–75 years), particularly for behavioral CVRF and abdominal obesity among men and for physiological CVRF among women (p<0.05).

Conclusion

Large absolute differences in the prevalence of CVRF according to education categories were observed in this Swiss population. The socioeconomic gradient in CVRF tended to be larger in women and in younger persons.  相似文献   

17.

Background

Annually, more than 27,000 persons die of cancer in the Czech Republic. It is known that in addition to the demographic aging of the Czech population, the cancer burden is increased.

Aim

These data clearly demonstrate the need for affordable and good follow-up care for patients, especially for older patients and/or patients with no other cancer treatment due to irreversible progression of tumor.

Materials and methods

We are talking about so-called palliative cancer care, which can be provided at different levels. One of the most common forms of palliative cancer care is hospice care.

Results

Our clinic in the years 2008–2010 received a total of 446 patients. 288 of them were women and 158 men. The average age of women was 61 years (age range 20–81 years). The average age of men was 56 years (age range 18–96 years). The performance status was in the fitness category PS-0 (8%), PS-1 (54%), PS-2 (33%) and PS-3 (5%).

Conclusion

Currently the outpatient palliative cancer care are coming more into the forefront. This type of care allows patients to stay as long as possible at home among their close relatives. Prerequisite for a well working outpatient palliative care is cooperation with general practitioners and home health care agencies.  相似文献   

18.
19.

Purpose

To examine the frequency and potential of dose-volume predictors for chest wall (CW) toxicity (pain and/or rib fracture) for patients receiving lung stereotactic body radiotherapy (SBRT) using treatment planning methods to minimize CW dose and a risk-adapted fractionation scheme.

Methods

We reviewed data from 72 treatment plans, from 69 lung SBRT patients with at least one year of follow-up or CW toxicity, who were treated at our center between 2010 and 2013. Treatment plans were optimized to reduce CW dose and patients received a risk-adapted fractionation of 18 Gy×3 fractions (54 Gy total) if the CW V30 was less than 30 mL or 10–12 Gy×5 fractions (50–60 Gy total) otherwise. The association between CW toxicity and patient characteristics, treatment parameters and dose metrics, including biologically equivalent dose, were analyzed using logistic regression.

Results

With a median follow-up of 20 months, 6 (8.3%) patients developed CW pain including three (4.2%) grade 1, two (2.8%) grade 2 and one (1.4%) grade 3. Five (6.9%) patients developed rib fractures, one of which was symptomatic. No significant associations between CW toxicity and patient and dosimetric variables were identified on univariate nor multivariate analysis.

Conclusions

Optimization of treatment plans to reduce CW dose and a risk-adapted fractionation strategy of three or five fractions based on the CW V30 resulted in a low incidence of CW toxicity. Under these conditions, none of the patient characteristics or dose metrics we examined appeared to be predictive of CW pain.  相似文献   

20.

Background

Shorter telomere length and poor sleep are more prevalent at older ages, but their relationship is uncertain. This study explored associations between sleep duration and telomere length in a sample of healthy middle and early old age people.

Methods

Participants were 434 men and women aged 63.3 years on average drawn from the Whitehall II cohort study. Sleep duration was measured by self-report.

Results

There was a linear association between sleep duration and leukocyte telomere length in men but not in women (P = 0.035). Men reporting shorter sleep duration had shorter telomeres, independently of age, body mass index, smoking, educational attainment, current employment, cynical hostility scores and depressive symptoms. Telomeres were on average 6% shorter in men sleeping 5 hours or fewer compared with those sleeping more than 7 hours per night.

Conclusion

This study adds to the growing literature relating sleep duration with biomarkers of aging, and suggests that shortening of telomeres might reflect mechanisms through which short sleep contributes to pathological conditions in older men.  相似文献   

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