Dementia "e"-consults for Behavioral and Psychological Symptoms of Dementia: Improving access to specialty dementia care for rural Veterans.

OBJECTIVES: This paper characterizes a telephone-based e-consult program designed to assess and treat behavioral and psychological symptoms of dementia (BPSD) for older rural Veterans. METHODS: E-consults required geriatricians to conduct chart review and telephone calls to caregivers to determine behavior triggers, prior management attempts, and medications. Pharmacologic and non-pharmacological recommendations were provided with follow-up calls as needed. RESULTS: Evaluation of 364 Veterans (M age = 80.8, 32% in rural/distal clinics) showed 97% (n = 355) of E-consult interventions included caregiver dementia education to prepare them for managing disease progression and provide non-pharmacological strategies for BPSD. Ninety-four percent (n = 244) of Veterans received medication guidance. A total of 37,504 travel miles was saved, with an average of 108 miles for each Veteran. CONCLUSIONS: Findings support continued implementation of telephone and other virtual modalities of assessing and treating BPSD for older Veterans, thereby increasing access to dementia specialists, especially for rural older adults and their caregivers. A limitation to e-consults is the time needed to provide services compared to the maximum workload credit allowed. CLINICAL IMPLICATIONS: Virtual care improves access to Geriatric specialists and semi-urgent care that otherwise is not available. E-consults are effective in providing primary care providers guidance for diagnosis and management of dementia.

Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

Implementation of a brief anxiety assessment and evaluation in a Department of Veterans Affairs geriatric primary care clinic.

Anxiety disorders are common and debilitating in older individuals, yet anxiety is often not formally assessed in primary care. We conducted a quality improvement project to examine the feasibility of implementing a brief anxiety assessment, the Geriatric Anxiety Inventory (GAI), in a Department of Veterans Affairs geriatric primary care clinic. We compared the GAI with a depression assessment, the 15-item Geriatric Depression Scale (GDS-15). Fifty older Veterans (mean = 78.5 +/- 7.4 yr) completed the GAI and GDS-15. Mean completion time and feedback to patients was brief (6.20 min; n = 10). Good internal consistency (alpha = 0.82) was found for GAI scores. Patients with psychiatric diagnoses obtained significantly higher GAI scores (mean = 4.73 +/- 1.15) compared with patients without psychiatric diagnoses (mean = 1.15 +/- 1.86, t(11.46) = -3.10, p = 0.01). Findings suggest that the GAI is acceptable to patients but may not be suitable for differentiating anxiety symptoms or disorders from depression. Interdisciplinary team members continued to implement the GAI after project completion to screen for and track anxiety symptoms in our geriatric primary care patients. Detecting anxiety with the GAI had the benefit of allowing providers to initiate conversations about available treatments and track symptoms as part of noting treatment progress.

Diabetes mellitus in centenarians.

OBJECTIVES: To describe the prevalence of diabetes mellitus (DM) in centenarians. DESIGN: Cross-sectional, population-based. SETTING: Forty-four counties in northern Georgia. PARTICIPANTS: Two hundred forty-four centenarians (aged 98-108, 15.8% male, 20.5% African American, 38.0% community dwelling) from the Georgia Centenarian Study (2001-2009). MEASUREMENTS: Nonfasting blood samples assessed glycosylated hemoglobin (HbA(1c)) and relevant clinical parameters. Demographic, diagnosis, and DM complication covariates were assessed. RESULTS: 12.5% of centenarians were known to have DM. DM was more prevalent in African Americans (27.7%) than whites (8.6%, P < .001). There were no differences between men (16.7%) and women (11.7%, P = .41) or between centenarians living in the community (10.2%) and in facilities (13.9%, P = .54). DM was more prevalent in overweight and obese (23.1%) than nonoverweight (7.1%, P = .002) centenarians. Anemia (78.6% vs 48.3%, P = .004) and hypertension (79.3% vs 58.6%, P = .04) were more prevalent in centenarians with DM than in those without, and centenarians with DM took more nonhypoglycemic medications (8.6 vs 7.0, P = .02). No centenarians with HbA(1c) of less than 6.5% had random serum glucose levels greater than 200 mg/dL. DM was not associated with 12-month all-cause mortality, visual impairment, amputations, cardiovascular disease, or neuropathy. Thirty-seven percent of centenarians reported onset before age 80 (survivors), 47% between age 80 and 97 (delayers), and 15% aged 98 and older (escapers). CONCLUSION: Diabetes mellitus is a risk factor for cardiovascular disease and mortality but is seen in persons who live into very old age. Aside from higher rates of anemia and use of more medications, few clinical correlates of DM were observed in centenarians.

The effect of doxazosin, finasteride and combination therapy on nocturia in men with benign prostatic hyperplasia.

PURPOSE: We evaluated the effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 3,047 men with lower urinary tract symptoms/benign prostatic hyperplasia enrolled in the Medical Therapy of Prostatic Symptoms trial were randomly assigned to receive doxazosin alone, finasteride alone, combination therapy or placebo. Treatment effectiveness was assessed according to intent to treat by mean reduction in self-reported nightly nocturia at 1 and 4 years. A subgroup analysis by age (younger than 70 vs 70 years old or older) was also performed. RESULTS: Of the men 2,583 reported 1 or more episodes of nocturia and finished 12 or more months of the trial. Mean nocturia was similar in all groups at baseline. Mean nocturia was reduced at 1 year by 0.35, 0.40, 0.54 and 0.58 in the placebo, finasteride, doxazosin and combination groups, respectively. Reductions with doxazosin and combination therapy were statistically greater than with placebo (p <0.05). At 4 years nocturia was also significantly reduced in patients treated with doxazosin and combination therapy (p <0.05 vs placebo). In men older than 70 years (495) all drugs significantly reduced nocturia at 1 year (finasteride 0.29, doxazosin 0.46 and combination 0.42) compared to placebo (0.11, p <0.05). CONCLUSIONS: Doxazosin and combination therapy reduced nocturia more than placebo, but the net benefit of active drug compared to placebo was often modest with a net difference of less than 0.20 fewer nightly nocturia episodes at 1 and 4 years. Findings in men 70 years old or older were similar, with an even smaller effect observed for finasteride.

Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone.

Testosterone (T) levels decline as men age, but it is unclear whether this has an effect on cognition. Some studies indicate that lower T levels are associated with memory loss; thus, maintaining a higher T level could have positive effects on aspects of cognitive function. Concerns exist, however, about the effect of T therapy on the prostate in older men. We hypothesized that T replacement in older men with low T levels would improve aspects of cognitive function and that the addition of finasteride would not affect the T-induced cognitive improvements. Healthy men, 65 to 83 years of age, with baseline total T below 350 ng/dL and no evidence of cognitive impairment were randomly assigned to 1 of 3 regimens: 200 mg of T every 2 weeks by intramuscular injection with placebo pill daily (T-only), 200 mg of T every 2 weeks by intramuscular injection with 5 mg of finasteride daily (T+F), or placebo injections and pills (placebo). Sixty-nine men completed baseline cognitive testing; 65 completed at least 4 months, and 46 completed all 36 months of the study. Participants were given a battery of cognitive evaluations at baseline, 4 months, and 36 months, along with measurement of serum hormone levels. Serum total T, bioavailable T, and estradiol levels in the T-only and T+F groups significantly increased throughout the treatment period, whereas these hormone levels did not change in the placebo group. Only minimally significant differences were seen among the 3 groups in any evaluation of cognitive performance, either in the short-term (4 months) or the long-term (36 months) analysis. These results indicate that T replacement, whether given alone or in combination with finasteride, for 36 months in healthy older men without cognitive impairment at baseline has no clinically significant effect on tests of cognitive function. Further studies are warranted to determine whether hormone replacement in men with preexisting cognitive impairment is beneficial.

Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study.

OBJECTIVE: This manuscript examines the relationships of total testosterone (T), bioavailable T, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) to measures of physical performance in a large, population-based, random sample of men. METHODS: In the most recent wave of the Massachusetts Male Aging Study, measures of strength and physical performance [seven-item physical performance test (PPT), timed chair stand test, and grip strength] were made in 684 men, aged 55-85 yr. Complete hormone data were also obtained. Initial graphical exploration of performance outcomes as a function of hormone levels showed linear increases in physical performance up to certain threshold hormone concentrations, beyond which the associations were diminished. Regression models were used to estimate threshold locations and standardized regression coefficients quantifying the association between hormones and strength. RESULTS: All hormones exhibited significant age-adjusted positive association with PPT score below, but not necessarily above, the thresholds. DHEA was positively associated with chair stand score below, but was not above the threshold. None of the hormones studied was significantly associated with grip strength. CONCLUSION: Up to certain critical concentrations, elevated levels of TT, total T, bioavailable T, DHEA, and DHEA sulfate are associated with increased physical performance, as indicated by the PPT. However, levels beyond those critical concentrations, as might be achieved through exogenous supplementation, do not appear to confer any additional benefit. In general, hormone concentrations do not appear to be meaningfully associated with grip strength or chair stand scores.

Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T.

Testosterone (T) therapy in older men with low serum T levels increases lean body mass and decreases fat mass. These changes might improve physical performance and strength; however, it has not been established whether T therapy improves functional outcome in older men. Moreover, concerns exist about the impact of T therapy on the prostate in older men. The administration of finasteride (F), which partially blocks the conversion of T to the more potent androgen, dihydrotestosterone, attenuates the impact of T replacement on prostate size and prostate-specific antigen. We hypothesized that T replacement in older, hypogonadal men would improve physical function and that the addition of F to this regimen would continue to provide the T-induced improvements in physical performance, strength, and body composition. Seventy men with low serum T (<350 ng/dl), age 65 yr and older, were randomly assigned to receive one of three regimens for 36 months: 1) T enanthate, 200 mg im every 2 wk, with placebo pills daily (T-only); 2) T enanthate, 200 mg every 2 wk, with 5 mg F daily (T + F); or 3) placebo injections and pills (placebo). We obtained serial measurements of timed physical performance, grip strength, lower extremity strength, body composition (by dual-energy x-ray absorptiometry), fasting cholesterol profiles, and hormones. Fifty men completed the 36-month protocol. After 36 months, T therapy significantly improved performance in a timed functional test when compared with baseline and placebo [4.3 +/- 1.6% (mean +/- sem, T-only) and 3.8 +/- 1.0% (T + F) vs. -5.6 +/- 1.9% for placebo (P < 0.002 for both T and T + F vs. placebo)] and increased handgrip strength compared with baseline and placebo (P < 0.05). T therapy increased lean body mass [3.77 +/- 0.55 kg (T-only) and 3.64 +/- 0.56 kg (T + F) vs. -0.21 +/- 0.55 kg for placebo (P < 0.0001)], decreased fat mass, and significantly decreased total cholesterol, low-density lipoprotein, and leptin, without affecting high-density lipoprotein, adiponectin, or fasting insulin levels. These results demonstrate that T therapy in older men with low serum T improves physical performance and strength over 36 months, when administered alone or when combined with F, and suggest that high serum levels of dihydrotestosterone are not essential for these beneficial effects of T in men.

Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone.

Older men, particularly those with low serum testosterone (T) levels, might benefit from T therapy to improve bone mineral density (BMD) and reduce fracture risk. Concerns exist, however, about the impact of T therapy on the prostate in older men. We hypothesized that the combination of T and finasteride (F), a 5 alpha-reductase inhibitor, might increase BMD in older men without adverse effects on the prostate. Seventy men aged 65 yr or older, with a serum T less than 12.1 nmol/liter on two occasions, were randomly assigned to receive one of three regimens for 36 months: T enanthate, 200 mg im every 2 wk with placebo pills daily (T-only); T enanthate, 200 mg every 2 wk with 5 mg F daily (T+F); or placebo injections and pills (placebo). Low BMD was not an inclusion criterion. We obtained serial measurements of BMD of the lumbar spine and hip by dual x-ray absorptiometry. Prostate-specific antigen (PSA) and prostate size were measured at baseline and during treatment to assess the impact of therapy on the prostate. Fifty men completed the 36-month protocol. By an intent-to-treat analysis including all men for as long as they contributed data, T therapy for 36 months increased BMD in these men at the lumbar spine [10.2 +/- 1.4% (mean percentage increase from baseline +/- SEM; T-only) and 9.3 +/- 1.4% (T+F) vs. 1.3 +/- 1.4% for placebo (P < 0.001)] and in the hip [2.7 +/- 0.7% (T-only) and 2.2 +/- 0.7% (T+F) vs. -0.2 +/- 0.7% for placebo, (P < or = 0.02)]. Significant increases in BMD were seen also in the intertrochanteric and trochanteric regions of the hip. After 6 months of therapy, urinary deoxypyridinoline (a bone-resorption marker) decreased significantly compared with baseline in both the T-only and T+F groups (P < 0.001) but was not significantly reduced compared with the placebo group. Over 36 months, PSA increased significantly from baseline in the T-only group (P < 0.001). Prostate volume increased in all groups during the 36-month treatment period, but this increase was significantly less in the T+F group compared with both the T-only and placebo groups (P = 0.02). These results demonstrate that T therapy in older men with low serum T increases vertebral and hip BMD over 36 months, both when administered alone and when combined with F. This finding suggests that dihydrotestosterone is not essential for the beneficial effects of T on BMD in men. In addition, the concomitant administration of F with T appears to attenuate the impact of T therapy on prostate size and PSA and might reduce the chance of benign prostatic hypertrophy or other prostate-related complications in older men on T therapy. These findings have important implications for the prevention and treatment of osteoporosis in older men with low T levels.

The androgen-deficient aging male: current treatment options.

All delivery forms of testosterone should be equally efficacious in treating the androgen-deficient aging male if adequate serum testosterone levels are obtained. The testosterone preparations available in North America include the oral undecanoate, injectable testosterone esters, the scrotal patch, the nonscrotal transdermal patch, and the transdermal gels. Selection of a specific testosterone preparation for replacement therapy depends on many factors, including the magnitude and pattern of serum testosterone levels produced, side effects of the particular formulation, reversibility if an adverse event should occur, convenience of use, cosmetic issues related to the preparation, and cost. In addition, potential adverse effects of testosterone therapy applicable to all forms of testosterone delivery, such as fluid retention, gynecomastia, polycythemia, worsening of sleep apnea, change in cardiovascular-disease risk, or alterations in prostate health, need to be considered both prior to therapy and during treatment monitoring.

Androgen deficiency in the aging male: when, who, and how to investigate and treat.

Androgen deficiency in the aging male (ADAM), also known as andropause, affects an estimated 1 in 200 men. The abnormally low levels of testosterone in these men can usually be managed with androgen supplementation therapy. Because a large proportion of urologic patients are men at or beyond middle age, urologists should be familiar with ADAM, its clinical manifestations, the rational approach to its diagnosis and treatment, and the consequences of treatment. Equally important is responsibility for the patient's monitoring, because prolonged androgen replacement therapy can be associated with significant complications, particularly in the prostrate.