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N Fleshner

Publications and source records attributed to N Fleshner.

At least 19 recordsLinked to original sources
PubMed2006

The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer--results from a 4-month pre-radical prostatectomy study.

BACKGROUND: As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5alpha-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS: Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS: Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of >or=90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS: Dutasteride treatment results in similar but less marked changes compared with androgen ablation.

5-alpha Reductase Inhibitors↗
PubMed2002

The role of serial free/total prostate-specific antigen ratios in a watchful observation protocol for men with localized prostate cancer.

OBJECTIVE: To examine the change in the free/total prostate specific antigen ratio (f/tPSA) with time and to assess the potential value of serial measurements of f/tPSA as a determinant of disease progression in untreated, low-to-intermediate grade prostate cancer (T1b-T2b N0M0, Gleason score < or = 7 and PSA < or = 15 ng/mL). PATIENTS AND METHODS: In a prospective single-arm cohort study from November 1995, patients were conservatively managed with watchful observation alone unless they met arbitrarily defined criteria (clinical, histological and biochemical) of disease progression. Patients were followed regularly and underwent blood tests including PSA and f/tPSA. The initial and mean f/tPSA and the rate of change of f/tPSA with time were evaluated against the rate constant for the PSA doubling time (PSATd). Correlation analyses were used to evaluate any association between baseline clinical variables and either the rate of change of f/tPSA or initial f/tPSA. RESULTS: As of December 2000, 161 of a total of 206 accrued patients had three or more f/tPSA measurements and formed the basis of the study (median age 70 years; median follow-up 2.7 years). The median initial f/tPSA was 0.16; there was a significant negative correlation between this value and the initial total PSA. The mean f/tPSA and rate of change of f/tPSA with time were significantly negatively correlated with the rate constant for PSATd. Also, the rate of change of f/tPSA correlated negatively with clinical T stage, but not with other baseline variables, including initial PSA, age and Gleason score. CONCLUSION: The f/tPSA in men with untreated, clinically localized prostate cancer varied widely. The negative correlation between the rate of change of f/tPSA with time and rate constant for PSATd suggests that both might provide valuable information to allow clinicians to develop a strategy for optimizing the timing of therapeutic intervention for those patients choosing watchful observation alone.

Adenocarcinoma↗
PubMed2001

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PURPOSE: To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. METHODS AND MATERIALS: A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. RESULTS: As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. CONCLUSION: Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

Adenocarcinoma↗
PubMed2001

The role of serial transrectal ultrasonography in a 'watchful waiting' protocol for men with localized prostate cancer.

OBJECTIVE: To determine the value of serial 6-monthly transrectal ultrasonography (TRUS) in a cohort of men with localized prostate cancer who consented to a programme of watchful waiting with selective delayed intervention. PATIENTS AND METHODS: Since November 1995, 180 men were accrued into an ongoing prospective study of watchful waiting with selective delayed intervention; 174 patients enrolled before 31 December 1999 comprised the cohort for the present study. The prospectively collected clinical data, including the TRUS reports, were reviewed systematically. Twenty-eight men met the arbitrarily predefined criteria of disease progression and required definitive treatment. The TRUS findings were scored as being consistent with the clinical scenario (i.e. clinical, biochemical or histological progression) if they reported a new or enlarging hypoechoic peripheral zone lesion, or a > or = 30% increase in overall prostate volume at the time of progression. In 136 men who had undergone two or more serial TRUS examinations the relationships between the rate of change of prostate-specific antigen (PSA) and changes in both gland volume and the number of hypoechoic lesions were also examined. RESULTS: The group of 28 men who progressed to require radical intervention underwent 83 TRUS examinations (median number per patient, three). Two men underwent TRUS only once at baseline because of progression within 6 months. Of these 28 men, only seven had changes on TRUS that were regarded as being consistent with progression; all seven consisted of the growth of an existing nodule or the appearance of a new nodule. In only one case was this accompanied by an increase of > or = 30% in gland volume. In the 136 men who underwent two or more serial TRUS examinations (median three, maximum nine), there was no correlation between the rate of change of PSA and changes in either gland volume or the number of peripheral zone hypoechoic lesions. CONCLUSION: The use of serial TRUS in men with known but untreated prostate cancer is of limited value as a determinant of disease progression.

Clinical Protocols↗
PubMed2000

Cigarette smoking patterns in patients after treatment of bladder cancer.

BACKGROUND: Assessment of smoking status and identification of those most likely to continue smoking are important in the management of patients who have bladder cancer, because continued smoking following diagnosis and treatment increases the likelihood of treatment-related complications, recurrence, second primary malignancies, and morbidity and mortality. METHODS: Patients (n = 224) receiving follow-up care of previously treated bladder cancers completed a brief written survey assessing their post-diagnosis smoking patterns. RESULTS: Despite the risks of continued smoking, 69% of the patients who had been active smokers at the time of diagnosis (n = 84) reported smoking at some point following the diagnosis and 45% reported smoking at the time of assessment. Patients diagnosed at earlier stages were more likely to continue smoking. Patients diagnosed at later stages were 2.80 times more likely to be continuous abstainers than those diagnosed sooner (95% CI, 1.08-7.25). CONCLUSIONS: The findings underscore the need to assess smoking status and provide smoking-cessation advice and counseling within routine comprehensive care of bladder cancer patients.

Adult↗
PubMed2000

Effect of soluble and insoluble fiber diets on serum prostate specific antigen in men.

PURPOSE: We assess whether high fiber diets influence serum prostate specific antigen (PSA) related to effects on serum sex hormone levels and fecal steroid excretion. MATERIALS AND METHODS: A randomized crossover controlled trial was performed on 14 healthy men with hyperlipidemia on 2 metabolic diets 4 months in duration with each containing foods high in soluble or insoluble fiber and approximately 25 to 30 gm. dietary fiber per 1,000 kilocalories. Serum PSA, free testosterone and estradiol, and fecal bile acid and neutral sterol excretion were evaluated. RESULTS: Mean serum PSA was lower with the soluble than the insoluble fiber diet (0.07+/-0.03 ng./ml., p = 0.035). No treatment difference was seen in free testosterone or estradiol, although the latter decreased significantly with the insoluble fiber diet (9+/-3 pmol./l., p = 0.004). After 16 weeks total fecal bile acid output was greater with the soluble (341+/-56 mg. daily) compared to the insoluble (203+/-35, p = 0.001) fiber diet but no differences were seen in fecal neutral sterol elimination. The treatment difference in fecal lithocholic acid output related to the difference in serum PSA (r = 0.57, p = 0.035). CONCLUSIONS: A small but statistically significantly lower serum PSA was seen in healthy men consuming soluble fiber, which was not related to changes in serum sex hormones but was related to the increased lithocholic acid output as a possible marker of increased fecal steroid elimination. The effect of soluble fiber on prostatic disease may warrant further investigation.

Adult↗
PubMed2000

Differences between urologists in the United States and Canada in the approach to prostate cancer.

PURPOSE: We examine differences in screening, detection, staging and treatment of prostate cancer between urologists in the United States and Canada. MATERIALS AND METHODS: An anonymous questionnaire was developed and mailed to 700 randomly selected American and 350 Canadian urologists. The 7 domains of prostate cancer management comprised screening/case identification, radical prostatectomy indications, staging evaluations, neoadjuvant therapy, nerve sparing techniques, postoperative management and treatment of biochemical recurrence. The Dillman method of questionnaire administration was used. All data were stratified by country and analyzed using the generalized chi-square test. RESULTS: Surveys were adequately completed by 45% and 79% of American and Canadian urologists, respectively. Practice experience and clinical volumes were not significantly different between the 2 cohorts. Overall, there were few differences in prostate cancer screening, staging, postoperative management, biochemical failure and use of neoadjuvant therapy. However, practicing American urologists tended to pursue more aggressive case finding practices, such as a higher age cutoff for prostate specific antigen testing (p = 0.0001) and more frequent use of transition zone biopsies (p = 0.0001). American urologists also displayed a tendency toward more liberal indication for extirpative surgery. They were more likely to perform radical prostatectomy in men older than 70 years, those with higher prostate specific antigen and those with node positive disease. Among both national cohorts there was considerable variation in management patterns for all domains of prostate cancer. Variation was most common among treatment of patients with adverse pathological conditions (positive margins, seminal vesicle involvement) and postoperative biochemical failure. Even when credible evidence exists (biopsy technique, preoperative staging) significant proportions of urologists in both countries continued to practice contrary to existing data. CONCLUSIONS: American and Canadian practice patterns for prostate cancer differ significantly only in the domains of case identification and surgical indications. In addition, considerable intra-national variation in practice patterns exists. These data highlight the necessity to support randomized clinical trials in prostate cancer.

Canada↗
PubMed2000

p53 nuclear accumulation is not associated with decreased disease-free survival in patients with node positive transitional cell carcinoma of the bladder.

PURPOSE: Although the majority of patients with node positive transitional cell carcinoma of the bladder have disease progression, a definitive subset is cured by surgery only. Nuclear accumulation of p53 has been associated with disease progression in patients with superficial transitional cell carcinoma and decreased survival in those with muscle invasive disease. We determined whether p53 status would predict survival in a cohort with nodal metastasis. MATERIALS AND METHODS: We explored the comprehensive database of all 199 radical cystectomies performed at our institution between July 1988 and September 1999. The 59 patients in this database with node positive pathology comprise our study. We performed immunohistochemical analysis of specimens using the MAB1801 antibody with greater than 20% lymph node and primary tumor nucleus staining deemed positive. Additional covariates measured included patient age, sex, pathological disease stage, adjuvant chemotherapy and nodal stage. Disease-free survival curves were generated for the various covariates and compared using the log rank test. The Cox proportional hazards technique was used to determine covariate adjusted p53 survival. RESULTS: In the cohort overall median disease-free survival was only 21 months, although 18% of patients were disease-free at 5 years. There was evidence of p53 nuclear accumulation in 54% of cases and complete agreement of nodal with bladder p53 nuclear accumulation. No significant baseline differences were noted in the covariates with respect to p53 nuclear accumulation. For stratum specific disease-free survival univariate and multivariate analyses revealed that only pathological stages p0-p2b versus p3-p4 (hazards ratio 2.86, p = 0.03), and nodal stages N2 versus N1 and N3 versus N1 (hazards ratio 3.84, p = 0.01 and hazards ratio 13.3, p = 0.0002, respectively) were significantly associated with prolonged disease-free survival, while p53 nuclear accumulation was not. CONCLUSIONS: Despite credible evidence for p53 nuclear accumulation prognostication in patients with in situ and invasive transitional cell carcinoma, this marker is not predictive of disease-free survival in node positive disease.

Aged↗
PubMed2000

A randomized phase 3 study of intraoperative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy.

PURPOSE: We determine if mapping of the cavernous nerve during radical prostatectomy using intraoperative cavernous nerve stimulation with tumescence monitoring results in improved erectile potency compared to conventional nerve sparing. MATERIALS AND METHODS: A prospective, randomized, single blinded study was performed on 61 patients at 6 centers. Patients had elected to undergo nerve sparing prostatectomy and had normal preoperative erectile function documented by the Sexual Function Inventory Questionnaire (SFIQ) and RigiScan parallel testing. Patients were randomized between conventional nerve sparing and nerve sparing assisted by the CaverMap Surgical Aid. paragraph sign In all patients neural continuity was assessed immediately after prostate removal by proximal cavernous nerve stimulation. All patients were blinded according to their allocation cohort. RESULTS: At 1 year there was substantial improvement in erectile function in the CaverMap group as measured by RigiScan. This group had a mean of 15. 9 minutes of greater than 60% nocturnal tumescence compared to 2.1 minutes in the conventional nerve sparing group (p <0.024). By SFIQ there was a nonsignificant trend to improved potency in the CaverMap group (71% versus 62%, p = 0.17). Of patients who had bilateral, unilateral and no response to stimulation after resection erectile function assessed by SFIQ recovered in 68%, 27% and 0%, respectively (p = 0.016). CONCLUSIONS: CaverMap assisted prostatectomy led to improved erectile function as assessed by RigiScan testing with no associated adverse events. A response to stimulation immediately after removal of the prostate accurately predicted return of erectile function.

Adult↗
PubMed2000

Nutritional aspects of prostate cancer: a review.

OBJECTIVES: The primary prevention of prostate cancer through nutritional modification is becoming a focus of attention as important relationships between diet and cancer are becoming evident. Relevant research is reviewed, along with recent data implicating various vitamin supplements and food products in the prevention and treatment of prostate cancer. METHODS: The epidemiology of prostate cancer, and current knowledge of prevention, screening, and progression of neoplasia is discussed. The current understanding of diet and its importance in primary and secondary prevention is explored. Literature searches were performed on MedLine using relevant keywords to find studies relating to prevention and treatment of prostate cancer using dietary methods. Of these, 104 published manuscripts were used. The search was limited from the year 1975 to the present. RESULTS: Incidence rates for prostate cancer vary according to diet and lifestyle. Several double-blind placebo-controlled clinical trials have shown that supplementation with selenium reduces cancer incidence. Inhibitory effects on the growth of in vitro prostate cancer cell lines have been observed with the administration of soy isoflavones, lycopenes from tomatoes, and vitamin D. Other compounds, such as calcium and fatty acids, have been linked to higher incidences of prostate cancer. CONCLUSIONS: Evidence exists that diet may play an important role in the primary prevention of prostate cancer. Further research is necessary to define the role that nutrition plays in the prevention or promotion of prostate cancer.

Calcium, Dietary↗
PubMed1999

Influence of smoking status on the disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma of the bladder.

BACKGROUND: The aim of this study was to assess the influence of tobacco exposure, at the time of diagnosis, on the disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma (TCC) of the bladder. METHODS: A retrospective cohort study was performed using the MSKCC Registry to identify all institutional cases of "noninvasive" TCC (n = 1632) between 1985 and 1995. After employing exclusion criteria, 286 cases of incident tobacco-associated superficial TCC were divided into 3 strata of tobacco exposure (127 ex-smokers, 51 quitters, and 108 continued smokers) by chart review and post hoc questionnaires (n = 82). Measured outcomes included recurrence free survival and survival free of adverse events (defined a priori as disease progression or other urinary tract TCC). RESULTS: There were no significant differences among ex-smokers, quitters, and continued smokers in terms of stage, grade, tumor size, multifocality, up-front bacillus Calmette-Guérin therapy, or median follow-up. Ex-smokers presented at a later age than individuals who continued to smoke. Post hoc questionnaires and chart reviews were compared in terms of smoking status at time of diagnosis, and reliability was excellent (kappa = 0.89). Multivariate analyses revealed diminished recurrence free survival among continued smokers versus quitters or ex-smokers. Univariate analyses revealed diminished adverse event free survival among continued smokers versus quitters or ex-smokers. Multivariate models assessing adverse event free survival revealed a similar trend (P = 0.06). CONCLUSIONS: Continued smokers experience worse disease-associated outcomes than patients who quit smoking. Smoking cessation should thus be employed as a tertiary prevention strategy for patients with superficial TCC.

Adult↗
PubMed1999

Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study.

Dietary intake of tomatoes and tomato products containing lycopene, an antioxidant carotenoid, has been shown in recent studies to reduce the risk of cancer. This study was conducted to investigate the serum and prostate tissue lycopene and other major carotenoid concentrations in cancer patients and their controls. Serum lipid and protein oxidation was also measured. Twelve prostate cancer patients and 12 age-matched subjects were used in the study. Significantly lower serum and tissue lycopene levels (44%, p = 0.04; 78%, p = 0.050, respectively) were observed in the cancer patients than in their controls. Serum and tissue beta-carotene and other major carotenoids did not differ between the two groups (p = 0.395 and p = 0.280, respectively). Although there was no difference (p = 0.760) in serum lipid peroxidation between cancer patients and their controls (7.09 +/- 0.74 and 6.81 +/- 0.56 mumol/l, respectively), serum protein thiol levels were significantly lower among the cancer patients (p = 0.026). This study demonstrates that the status of lycopene but not other carotenoids in prostate cancer patients is different from controls. The role of dietary lycopene in preventing oxidative damage of biomolecules and thereby reducing the risk of prostate cancer needs to be evaluated in future studies.

Aged↗
PubMed1999

A phase 1-2 trial of diethylstilbestrol plus low dose warfarin in advanced prostate carcinoma.

PURPOSE: This prospective study was designed to determine the safety and efficacy of low dose warfarin in the prophylaxis of thromboembolic disease in patients receiving diethylstilbestrol therapy for advanced prostatic carcinoma. MATERIALS AND METHODS: Patients were stratified to receive 1 mg. warfarin and 3 mg. diethyl-stilbestrol daily (younger than 65 years) or 1 mg. warfarin and 2 mg. diethylstilbestrol daily (older than 65 years). Efficacy of therapy was determined by measuring serum prostate specific antigen (PSA), testosterone and international normalized ratio. Patients were monitored for signs and symptoms of hypercoagulability, bleeding and fluid retention. RESULTS: Of the 32 patients enrolled in the study 6 were lost to followup and 4 died of advanced prostatic disease (2), pneumonia (1) and myocardial infarction (1). Patients were followed for a total of 272 months. Median patient age was 73.5 years. Median pretreatment serum PSA was 95.4 microg./l. with a median pretreatment serum testosterone value of 12.9 nmol./l. After 3 months of therapy the median serum PSA was 1.5 microg./l. with a median serum testosterone value of 0.1 nmol./l. Adverse events were common. In 10 patients (31%) clinically significant proximal deep venous thrombosis developed, 2 (7%) had a myocardial infarction, 2 (7%) had transient ischemic attacks, 1 had new prolonged chest pain and 1 had marked dyspnea due to congestive heart failure. Clotting factor assays performed in a subset of 7 patients demonstrated that factor VII failed to normalize. CONCLUSIONS: The significant thromboembolic toxicity associated with the hypercoagulable state induced by diethylstilbestrol is not reduced by fixed low dose warfarin therapy.

Adult↗
PubMed1999

Prevalence and patterns of the use of complementary therapies among prostate cancer patients: an epidemiological analysis.

PURPOSE: We determine the prevalence and patterns of the use of complementary therapies among patients with and those at high risk for prostate cancer. MATERIALS AND METHODS: A cross-sectional survey was performed of men presenting to 2 urban tertiary urology clinics for prostate cancer evaluation or followup, and those attending a prostate cancer support group. All men diagnosed with and those at high risk (positive family history or abnormal prostate specific antigen) for prostate cancer were eligible for study. A 9-item self-administered, anonymous questionnaire about complementary therapies was administered. RESULTS: Of 357 patients who received the survey 155 from the urology clinics and 113 from the support group responded, for a total response rate of 75%. Of the patients presenting to urology clinics and the support group 27.4 and 38.9% with and 25.8 and 80% at high risk for prostate cancer, respectively, used some form of complementary therapy. The use significantly differed according to disease status (p = 0.001), and was highest among men who were clinically disease-free after radical therapy. Of the patients 24% did not inform the urologist of using alternative therapy. CONCLUSIONS: The prevalence of the use of complementary therapy among patients with or at increased risk for prostate cancer was high and dependent on the disease state. Urologists should be aware of this pattern of use, and consider the potential effects when assessing patients for and with prostate cancer.

Aged↗
PubMed1999

Vitamin E inhibits the high-fat diet promoted growth of established human prostate LNCaP tumors in nude mice.

PURPOSE: Prostate cancer has become an important public health problem in the Western world. It is currently the most common diagnosed cancer and the second leading cause of cancer deaths among North American men. Prostate cancer possesses a unique descriptive epidemiology which suggests that environmental factors (such as dietary fat consumption) play a pivotal role in tumor progression. Data from our institution have demonstrated that diets high in fat content can accelerate the growth of human LNCaP prostate cancer cells. One of the hypothesized mechanisms of dietary fat induced growth is oxidative stress. Our purpose was to determine the effect of supplemental Vitamin E, a potent intracellular antioxidant, on the high-fat promoted growth of transplanted LNCaP cells in the athymic mouse. MATERIALS AND METHODS: Tumors were induced by subcutaneous injection of 10(6) LNCaP cells. Mice were fed a control diet consisting of 40.5% of total calories from dietary fat. Once tumors were formed, PSA values were obtained and animals were randomized into 4 groups of 12. The animals were then assigned to one of 4 dietary plans. Group 1 received the control diet of 40.5%-kcal fat. Group 2 received the 40.5%-kcal fat diet plus supplemental Vitamin E. Group 3 received a diet of 21.2%-kcal fat. Group 4 received the 21.2%-kcal fat diet plus supplemental Vitamin E. Food intake, animal weights, and tumor volumes were recorded weekly. Survival analyses with time to a target volume of 0.523 cm.3 (defined as failure) were used to compare tumor growth among the 4 groups. Two-sided tests (log rank test) with alpha set at 0.05 were used to determine significance. RESULTS: Tumor growth rates were highest in the animals fed a 40.5%-kcal fat diet (p <0.05 group 1). Tumors in animals fed 40.5%-kcal fat plus Vitamin E, 21.2%-kcal fat, and 21.2%-kcal fat plus Vitamin E, experienced statistically indistinguishable growth rates. No significant differences were noted in total ingested calories, animal weight gain or initial PSA levels. CONCLUSIONS: These data suggest that the mechanism of dietary fat induced growth of human prostate cancer cells is mediated by oxidative stress. It also raises the possibility of a therapeutic benefit of vitamin E in preventing prostate cancer.

Animals↗
PubMed1996

The artificial urinary sphincter for post-radical prostatectomy incontinence: impact on urinary symptoms and quality of life.

PURPOSE: We addressed the impact of the artificial urinary sphincter on the health related quality of life and urinary symptoms in men with post-radical prostatectomy incontinence. MATERIALS AND METHODS: A total of 30 men with an AMS800 artificial urinary sphincter following radical prostatectomy responded to a questionnaire dealing with the impact of the symptoms on activities of daily living and quality of life. We compared these results to those of 31 patients who underwent radical prostatectomy but did not require an artificial urinary sphincter. RESULTS: Incontinence was minimal in both groups. Irritative symptoms were noted in the artificial urinary sphincter group, as well as some impairment in activities of daily living. No significant differences were noted with respect to quality of life. CONCLUSIONS: The artificial urinary sphincter is an effective form of therapy for post-radical prostatectomy incontinence but irritative voiding symptoms occur, which tend to limit activities of daily living.

Activities of Daily Living↗